Eye, Retina, and Visual System of the Mouse

EYE, RETINA, AND VISUAL SYSTEM OF THE MOUSE

Edited by Leo M. Chalupa and Robert W. Williams

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Library of Congress Cataloging-in-Publication Data Eye, retina, and visual system of the mouse / Leo M. Chalupa and Robert W. Williams, editors. p. cm. Includes bibliographical references and index. ISBN 978-0-262-03381-7 (hardcover : alk. paper) 1. Mice—Sense organs. 2. Eye. 3. Visual pathways. I. Chalupa, Leo M. II. Williams, Robert W., 1952– QL737.R6E94 2008 573.8′819353—dc22 2007047445 10 9 8 7 6 5 4 3 2 1 INDEX

Note: Page numbers followed by f indicate ﬁ gures; page numbers followed by t indicate tables.

A taste ability in, 23 gain and response axis of, adaptation of, visual acuity of, 20 96–98, 97t A and A/J strain Albinism, retinal ganglion cell projections Anophthalmic mice, 269, 271 auditory evoked brainstem response in, 22 and, 397 Anterior chamber, cell types in, 644–645 conditioned taste aversion in, 29 Albino mice, 61 Anterior chamber–associated immune hearing and visual abilities in, 15t, 16 pattern discrimination in, 18 deviation (ACAID), 521–522 mutation and effect in, 62t visual acuity of, 20 pigmentary glaucoma and, 483 pattern discrimination in, 18 Aldose reductase, diabetic retinopathy and, Antiangiogenic gene therapy, 607 taste ability in, 24 552 Antibodies, against neurofi lament H, as visual acuity of, 20 Alleles. See also specifi c alleles retinal ganglion cell marker, 193 ABCA4 mutations, 723 defi ning disease progression, clinical Antigen-presenting cells (APCs), Abca4/Abcr null mutant mice, Stargardt outcome, or important domains, experimental autoimmune uveitis macular degeneration in, 540–542, 650 and, 519 541f defi ning response to treatment, 651 Anxiety-related behavior tasks, 29 Ablation, targeted, to assess role of defi ning responses to environmental AP1, in cornea and lens development, 703 photoreceptors, 595–596 infl uences, 650–651 AP2, in cornea and lens development, 703 ab-LIM, directed growth of retinal ganglion phenotypic variation due to, 649–651 AP2α, lens development and, 277 cell axons toward optic disc and, 384 Allen Brain Atlas, search of, for RALDH3 AP2α-Cre mice, 275 AC Master, 78, 78f colocalized genes, 370–371, 372f Apo-cellular RBP (CRALBP), 724 Acanthamoeba infections, 508–509 All-trans-retinol dehydrogenase, in visual Apoptosis. See Cell death αA/CAT transgenic mice, 273 cycle, 722–723 Aquaporin, cataracts and, 495 Achromatopsia, gene replacement therapy Amacrine cells Aqueous humor for, 612–613 cholinergic (starburst) infl ow of, 129, 129f Acoustic startle test, 22 mosaic architecture of, 150–151, 151f outfl ow of, 129–131 Adenoassociated virus (AAV) gene therapy, study approaches for, 598 uveoscleral, 132–133 605–614 dopaminergic Astrocyte(s) antiangiogenic, 607 genetic labeling of, 597–598 in optic nerve, 201–202, 202f for choroidal neovascularization, 610 mosaic architecture of, 151–153 retinal vascularization and, 287 future directions for, 613–614 gap junctions of, 167 Astrocyte progenitor cells (APCs), 390, gene replacement strategies and, 610–613 glucagon, in mouse versus chicken eye, 390f for functional defects in retina, 611–613 82–83 Atoh7, retinal ganglion cell development for structural defects in retinal disease, transgenic mice for study of, 597–598 and, 194 610–611 V-amacrine, 597 ATP-binding cassette A4, in visual cycle, for retinal neovascularization, 607, AMPA, excitatory lateral geniculate nucleus 723 609–610 responses and, 420, 422 Atropine, myopia development and, 83 vectors for, 605–607, 606t, 608t–609t AMPA receptors (AMPARs), 223–225 Auditory evoked brainstem response (ABR), Advanced glycation end products (AGEs), long-term depression and, 470 20, 22 diabetic retinopathy and, 552 in reticulogeniculate synapses, 431, 439 Autism spectrum disorders, visual cortical African pygmy mice, 3, 5, 8 Anaphase-promoting complex (APC), retinal functions in, 245 Age-related eye diseases, 581–588 ganglion cell axon growth ability and, Autoimmune uveitis. See Experimental cataracts as, in human and mouse eyes, 408 autoimmune uveitis (EAU) 588 Anesthesia dolorosa, model of, 25 Automated visual responses, measures of, in mice, search for, 581–582, 583t–584t Angioblasts, 285 111–115, 114f, 115f mouse models for, 581 Angiogenesis, 285–286, 639–641 Avoidance conditioning, active and passive, Age-related macular degeneration (AMD) hyaloid vessel regression versus, in norrin 27–28 gene therapy for, 607 defi cient mice, 532, 533f a-waves, cone, 138 in human and mouse eyes, 582, 584–588 sprouting, failure in, in norrin defi cient Axial length, changes in, measurement, Age-related retinal degeneration (ARRD), in mice, 531–532 77–79, 78f human and mouse eyes, 582, VEGF-A in, 640–641 Axons, of retinal ganglion cells. See Retinal 584–588, 585f–587f, 585t Angiopoietin, diabetic retinopathy and, ganglion cells (RGCs) Akita mice, diabetes in, 549 552–553 retinal neurodegeneration induced by, 551 Angiopoietin/Tek system, retinal B AKR/J strain vascularization and, 292 auditory evoked brainstem response in, Angiostatin, anti-angiogenic properties of, Bacterial artifi cial chromosome (BAC) 22 610 transgenesis, 594, 594f hearing and visual abilities in, 15t, 16 Angular vestibulo-ocular refl ex (aVOR), Bacterial infections, 506–508 pattern discrimination in, 18 88–91, 89f, 90f Bagg, Halsey J., 13

737 BALB strains, 62t synaptic transmission in outer retina Cadherin4, retinal vascularization and, 287 BALB/c and, 176f, 176–179, 177t Calcium anxiety-related behavior tasks and, 29 gap junctions of, 167 retinal ganglion cell axon growth ability auditory evoked brainstem response in, hyperpolarizing, 136 and, 408 22 synaptic transmission in outer retina synaptic transmission in outer retina and, conditioned odor preference in, 28 and, 176f, 176–179, 177t 177–178 learning and memory in, 27 ON and OFF pathway segregation and, Calcium currents, in dorsolateral geniculate pain sensitivity in, 25 353–354, 357 nucleus, 220 photoreceptor response damage by light in Rb-deﬁ cient retinas, 315 Calcium imaging and, 575, 577 role of gap junctions in, transgenic mice to of direction-selective retinal ganglion cell BALB/cByJ study, 596–597 responses, 598

hearing and visual abilities in, 15t, 16 synaptic output of, control by GABACR- for retinal wave measurement, 343 pattern discrimination in, 18 mediated inhibition, 182–183 with two-photon microscopy, for ocular visual acuity of, 20 Birdshot retinochoroidopathy, 516 dominance plasticity assessment, BALB/cJ Blind-sterile mutant, 501 441–442, 442f conditioned taste aversion in, 29 Bmp4, lens development and, 276 Calmodulin kinases (CaMKs), retinal hearing and visual abilities in, 15t, 16 Bmp7, lens development and, 276 ganglion cell axon growth ability and, pain sensitivity in, 25 Bone morphogenic protein (BMP) receptor 408 pattern discrimination in, 18 1b, targeting of retinal ganglion cell cAMP, retinal ganglion cell axon growth visual acuity of, 20 axons to optic disc and exit from eye ability and, 408 Barnes maze, 27 and, 385 cAMP response element–binding protein Basic ﬁ broblast growth factor (bFGF), retinal Brain (CREB), retinoic acid and, 366 ganglion cell axon growth and, 401 electroporation and, 626 Candida albicans infections, 508 Batten disease, 612 environmental enrichment and, 450 Capecchi, Mario R., 35 Bcl-2 retinoic acid actions in, 364–365 Carbohydrates, protein-bound, cataracts Bcl-2-overexpressing retina, 152 Brain Gene Expression Map (BGEM), and, 499–500 cell death and, 337f, 337–338 search of, for RALDH3 colocalized Carrageenan, subcutaneous injections of, 25 retinal neovascularization and, 293 genes, 370 Caspases, cell death and, 338 Beaded ﬁ laments, 499 Brain-derived neurotrophic factor (BDNF) CAST/Ei strain, taste ability in, 23 Behavior, environmental enrichment and, acceleration of visual system development CAST/EiJ 450 and, environmental enrichment hearing and visual abilities in, 15t Behavioral studies of mouse vision, 107–116 compared with, 453, 454 pattern discrimination in, 18 applied measurement of, 115–116, 116f cell death and, 336 Cat3, 501 idiosyncrasies associated with whole environmental enrichment and, increase Cat5, 501 animal behavior and, 108–109 due to, 457–458 Cataracts measures of, 109–115 retinal ganglion cell axon growth and, 401 age-related, in human and mouse eyes, of automated visual responses, 111–115, Brief-access taste test, 24 588 114f, 115f Brightness detection, measurement of, 16, gene expression leading to formation of, of visual perception in reinforcement- 17f, 18 273 based tasks, 109–111, 111f–113f Brn-3b, chiasm patterning and, 396–397 genetics of, 493–501 rationale for, 107–108 Brn-3b−/− mice, retinal ganglion cell axon mouse models for metabolic cataracts Behavioral tasks, for sensory function growth ability and, 407–408 and, 499–500 measurement, 15t, 15–16 Brn-3b−/− Brn-3c−/− mice, retinal ganglion cell mouse models for senile cataracts and, future directions for use of, 30 axon growth ability and, 407–408 500 of hearing, 20, 22 Brn-3c, chiasm patterning and, 397 mutations affecting lens membranes learning and measurement tasks and, Brn-3.2, directed growth of retinal ganglion and, 495–496 25–29 cell axons toward optic disc and, mutations affecting structural proteins of olfaction, 22–23 383–384 of lens and, 496–499 of pain sensitivity, 24–25 Bruch’s membrane, plate 64 mutations at early stages of lens of tactile and vibrissae sensitivity, 24 BUB strain, mutation and effect in, 62t development and, 493–494, 494f of taste, 23–24 BUB/BnJ pattern electroretinography and, 124 of vision, 16–20 auditory evoked brainstem response in, β-Catenin, inhibition of lens induction by, BEN, directed growth of retinal ganglion cell 22 277–278 axons toward optic disc and, taste ability in, 23 Caviness, Vernon, 245 382–383 Buried food test, 22 CBA strains, 13 Bfsp1, cataracts and, 499 b-waves, cone-driven, 137, 137f avoidance learning in, 28 Bfsp2, cataracts and, 499 BXD Genetic Reference Panel of Mice, CBA/Ca, anxiety-related behavior tasks bHLH transcription factors, retinal 664–665, 666t, 667 and, 29 development and, 303 BXSB strain, pattern discrimination in, 18 CBA/CaJ, auditory evoked brainstem BH3-only protein, cell death and, 338 response in, 22 Binocularity, in primary visual cortex, C CBA/J 49–51, 50f cued and contextual fear conditioning transcallosal cells and, 50–51 C strain, 13 in, 27 Bipolar cells Cacna 1a mutations, 100–101 learning and memory in, 26, 27 Clomeleon in, 597 CaCna1f nob2 mice, retinal ganglion cell tactile sensitivity in, 24 depolarizing, 136 responses in, 179–181, 180f taste ability in, 23

738 index CBA strains (continued) Cell type–specifi c promoters model for, 257, 258t, 259, 259f, 260f learning and memory in, 27 lineage tracing in retina using, plate 60 individual variation and observational mutation and effect in, 62t multicolor labeling of retina using, plate error and, 260–261 C57BL/6 and C57BL/6J strain, 59 technical and qualitative evaluation of 271–272 spatial regulation of gene expression using, model’s predictions and, 259–261 anxiety-related behavior tasks and, 29 plate 58 mouse models for, 262–263 auditory evoked brainstem response in, Cell-labeling techniques, for study of retinal scaling of eye and cortex and, 263–264 22 ganglion cells, 599 variability of mouse strains and, 262 circadian photoentrainment and, 210 Cellular retinaldehyde-binding protein Chung peripheral nerve injury model, 25 conditioned odor preference in, 28 (CRALBP), in visual cycle, 726 Chx10, retinal development and, 303 cones of, anatomy of, 135–137 Cellular retinol-binding protein type 1 Chx10-Cre;RbLox/− mice diabetes-induced retinal (CRBP1), in visual cycle, 725 retinal synaptogenesis in, 317–318, 318f neurodegeneration in, 551 Central nervous system. See also Brain rod development in, 313–314 hearing and visual abilities in, 15t, 16 plasticity of, pattern electroretinographic Chx10-Cre;RbLox/+ mice, retinal synaptogenesis learning and memory in, 27 measurement of, 121–122 in, 317 mutation and effect in, 62t Central retinal artery (CRA), anatomy of, Chx10-Cre;RbLox/Lox mice, rod development in, olfactory ability in, 22, 23 203–204, 204f 314 pain sensitivity in, 25 Central retinal vein, anatomy of, 204 Chx10-Cre;RbLox/Lox;Z/AP mice, rod pattern discrimination in, 18 Centrifugal model of evolution, 6, 7f development in, 315 as standard strain, 62 cGMP, retinal ganglion cell axon growth C12I strain, 13 tactile sensitivity in, 24 ability and, 408 Ciliary body, position of, aqueous humor taste ability in, 23, 24 C3H strains, 13 outfl ow and, 129 visual acuity of, 20 avoidance learning in, 28 Ciliary epithelium C57BL/6NCrlBR strain conditioned taste aversion in, 29 nonpigmented, 129 conditioned odor preference in, 28 mutation and effect in, 62t structure of, 129 pattern discrimination in, 18 C3HeB/FeJ strain, visual acuity of, 20 Ciliary muscle, 129 C57BL/10 strain, 271–272 C3H/HeIbg strain, cued and contextual fear Ciliary neurotrophic factor (CNTF), 613 C57BR/cdJ strain, auditory evoked conditioning in, 27 retinal ganglion cell axon growth and, brainstem response in, 22 C3H/He and C3H/HeJ strain 401 CCCTC binding factor, eye fi eld anxiety-related behavior tasks and, 29 Ciliary processes, 129, 130f transcription factor regulation by, auditory evoked brainstem response in, 22 Circadian behavior, mouse models for, 215 301 hearing and visual abilities in, 15t, 16 Circadian photoentrainment, 207–215 CCL2 protein, cell death inhibition by, 122, learning and memory in, 26, 27 circadian behaviors in mice and, 207–209, 123f pain sensitivity in, 25 208f CD-1 outbred strain pattern discrimination in, 18 circadian photoentrainment pathway conditioned odor preference in, 28 tactile sensitivity in, 24 neuroanatomy and, 209–210 olfactory ability in, 22, 23 taste ability in, 23 intrinsically sensitive retinal ganglion cells pattern discrimination in, 18 visual acuity of, 20 and, 211–212 CD18, diabetic retinopathy and, 553 Chase, Herman, 269 morphology, ontogeny, and functional Cell adhesion molecules (CAMs), retinal Chemical nociception, measurement of, 25 diversity of, 211–212, 212f ganglion cell axon guidance through CHI strain, 13 melanopsin and, 213–214 visual pathway and, 393 Chlamydia trachomatis infections, 508 phototransduction mechanism and, Cell cycle progression, in retinal progenitor Cholera toxin β subunit (CTB), development 213–214 cells, Math5 and, 324 of eye-specifi c segregation in lateral melanopsin-expressing retinal ganglion Cell death geniculate nucleus and, 418 cell role in circadian of developmental cells, retinal ganglion Cholesterol metabolism, cataracts and, 500 photoentrainment and, 210–211 cells and, 122 Cholinergic amacrine cells molecular basis of, 214f, 214–215 of endothelial cells, oxygen-induced mosaic architecture of, 150–151, 151f mouse as model system for human retinopathy and, 293 study approaches for, 598 circadian rhythm and, 207 of horizontal cells, 149 Chondroitin sulfate proteoglycans (CSPGs) photosensitivity and, 209 in mouse retina, 333–339 control of initial retinal ganglion cell axon target brain regions innervated by contribution to shaping of retinofugal outgrowth polarity and, 381 intrinsically photosensitive retinal and retinal circuits, 334–336, 335f ocular dominance plasticity and, 454–455 ganglion cells and, 212f, 212–213 major phases of, 333–334, 334f Choriocapillaris, plate 64 C57L/J strain, auditory evoked brainstem molecules involved in signaling, Choroidal circulation, oxygen delivery to response in, 22 regulating, and executing, 336–339, retina and, 560–561 C58/J strain, tactile sensitivity in, 24 337f Choroidal neovascularization, gene therapy Clock gene, 65 neurotrophic hypothesis of, 336 for, 610 Clomeleon, in bipolar cells, 597 of retinal ganglion cells, 333, 334 Chromatin, rod development and, 317 Cloning of genetic modifi ers, 653–655 in glaucoma, 485–487, 487f, plate 33, Chronology of mouse visual system chromosomal localization of modifi ed plate 34 development, 257–264 traits and, 653–654 matching sizes of interconnected comparison with development in rhesus gene expression profi ling and, 654–655 neuronal populations and, 335, macaque, 261 haplotype analysis and, 654 335f future research directions for, 264 microarray analysis and, 654–655 molecules involved in signaling, human developmental timing versus, modifi er screens using mutagenesis and, regulating, and executing, 337, 338 261–262, 262f 655

index 739 Cloning of genetic modifi ers (continued) retinal gap junctions and, 165 posttranslational modifi cation of, 715, segregating crosses with multiple strains of amacrine cells, 167 716 and, 654 of bipolar cells, 167 lens development and, 272 c-Maf, lens fi ber differentiation and, 278 of ganglion cells, 169, 171 α-Crystallins Coats’ disease, 528 of horizontal cells, 167 αA-crystallin structure and, plate 67 Cochlear vasculature, abnormalities of, in of photoreceptors, 165–166 cataracts and, 496, 496f Ndph knockout mice, 533–534 in proximal rod pathways, 167–169, expression in lens, 703–704, 712f, Cognitive functions, higher order, vision in 168f 712–713 tasks evaluating, 25 retinal waves and, 347 β-Crystallins Collagen I, primary open-angle glaucoma Cornea cataracts and, 497 and, 482 development of, 697, 698f expression in lens, 704, 713 Color blindness, gene replacement therapy transcription factors involved in, 699f, τ-Crystallins for, 612–613 699–703, plate 66 cataracts and, 497–498, 498f Commensal mice, 5 gene expression in. See Gene expression, expression in lens, 704, 713 Compensatory eye movements, 87, 88 in cornea and lens Cued and contextual fear conditioning, 27 adaptive properties of, 96–99, 97t, 98f, neovascularization of, matrix Cued platform task, for measuring visual 99f, 100 metalloproteinase-9 and, 506 perception, 110 Complete Freund’s adjuvant (CFA), refractive power of, 73 Curare, retinal wave blocking by, 345 experimental autoimmune uveitis Corpus callosum, visual cortex connections Current-clamp recordings, for retinal wave induced by, 515, 520 with, 46–47, 47f measurement, 343 Conditioned odor preference, 28 Coulombre, Alfred and Jane, 269 Cx36 expression, by photoreceptors, plate Conditioned taste aversion, 28–29 Cre expression, in Le-Cre, MLR10, and 5 Cone(s), 135–144. See also Photoreceptors MLR39 strains, plate 12 Cyclooxygenase-2 (COX-2) inhibitors, anatomy of, 135–137 Cre recombinases herpes simplex virus infection and, numerosity and retinal disposition and, cell type–specifi c regulation using, 506 135–136, 136f, plate 2 626–627, 629, 630f CYP1B1 retinal connectivity of cones and, 136 conditional gene alterations using, primary congenital glaucoma and, 483 S- and M-opsins and, 136–137 274–275, 275f primary open-angle glaucoma and, 482 ultrastructure and, 136 conditional RNAi and, 629–630, 632f Cytomegalovirus infections, murine, 509 damaging of, by rod dysfunction, 566 temporal and cell–type specifi c regulation Cytoskeletal proteins, cataracts and, dim-fl ash responses of, plate 3 using, 629, 631f 498–499 electroretinographic studies of, 137–139 temporal regulation using, 626, 627f, plate a-wave and, 138 57 D b-wave and, 137, 137f Cre-lox recombinase system functional coexpression of S- and for drug-controlled gene expression, 600f, DBA/2HaSmn strain, auditory evoked M-opsins and, 138–139 600–601 brainstem response in, 22 phenotypes of mice with cone for site-specifi c recombination, 599–600 DBA, DBA/2, and DBA/2J strain, 13 phototransduction genes inactivated Cre-lox-P system, 274 anxiety-related behavior tasks and, 29 and, 138, 138f Critical periods, experience-dependent auditory evoked brainstem response in, rapid recovery from bleaching stimuli plasticity and, 473 22 and, 138 Cross-axis adaptation, 98–99, 99f conditioned odor preference in, 28 functions of, 135 Crx, rod development and, 316 cued and contextual fear conditioning in, gap junctions of, 165–166, 166f Cry, circadian photoentrainment and, 214, 27 of mouse compared to other mammalian 214f as glaucoma model, pattern species, 36 Cry−1− mice, circadian photoentrainment and, electroretinogram application in, Nrl −/−, 139, 141–144 215 122–124, 123f caveats for investigations of, 142 Cry−2− mice, circadian photoentrainment and, hearing and visual abilities in, 15t, 16 electrophysiological recordings and, 215 learning and memory in, 27 141–142, 143f Cryaa mutation and effect in, 62t histochemical and ultrastructural cataracts and, 496, 496f, 588 pain sensitivity in, 25 evidence and, 141, 142t mutations of, plate 37 pattern discrimination in, 18 prospects for studies using, 143–144 Cryab, cataracts and, 496 pigment dispersion syndrome in, 483–485, role in scotopic visual pathway, targeted Cryba1, cataracts and, 497 484f ablation to assess, 595–596 CRYBB2, cataracts and, 497 melanosome contribution to, plate 32 scaling of, 263 Crybb2, cataracts and, 497 tactile sensitivity in, 24 single-cell recordings and, 139, 140f–142f Cryg taste ability in, 24 spatial vision and, 81–82 cataracts and, 497–498, 498f visual acuity of, 20 Cone pedicles, 136 mutations of, plate 38 DBA/2NCrlBR strain Cone synapses, 136 CRYGC, cataracts and, 498 conditioned odor preference in, 28 Cone visual cycle, 727, 728f, plate 69 CRYGD, cataracts and, 498 pattern discrimination in, 18 Congenital stationary night blindness CRYGD-P23T mutation, cataracts and, db/db mice (CSNB), 650 498 diabetes in, 550 Connective tissue, in optic nerve, 202, 203f Crystallins diabetes-induced retinal Connexins expression in cornea, 705 neurodegeneration in, 551 in lens, cataracts and, 495–496, 496f in lens, 703–704, 704f, 711–713, 716, Delayed-type hypersensitivity (DTH) as retinal ganglion cell markers, 193 716f responses, 505

740 index Dendritic arborization, Cre-lox recombinase retinogeniculate inputs and temporal early-life stimulation effects on neuronal system for study of, 601 information and, 223–225 and behavioral development and, Dendritic cells, antigen-pulsed, experimental retinal projections to, 40, 44–45 450–451 autoimmune uveitis induced by Dräger, Ursula, 245 neural consequences of environmental injection of, 516 Drug-controlled gene expression enrichment and, 450 Dendritic outgrowth, of horizontal cells, 150, Cre-lox recombinase system for study of, visual system development and, 150f 600f, 600–601 451–459, 452f, 454f, 455f, 457f, Depolarizing bipolar cells (DBCs), 136 reversible, 601 459f, plate 28, plate 29, plate synaptic transmission in outer retina and, 30 176f, 176–179, 177t E temporal phases during development Depth of fi eld, measurements of, 80, 80f controlled by environmental richness Developmental glaucoma, 483 Early-life stimulation, neuronal and and, 458, 459f Diabetes, adherence in retinal behavioral development and, Enzyme replacement therapy, 639 microvasculature of diabetic mouse, 450–451 EphB2, targeting of retinal ganglion cell plate 47 Efnb2, retinal vascularization and, 288 axons to optic disc and exit from eye Diabetic retinopathy, 547–554 Egr-1 knockout, refractive errors in, 83 and, 383f, 383–385 biochemical changes in mouse retinal Egr-1 mRNA, regulation of, 82 EphB3, targeting of retinal ganglion cell contributing to development of, Eicosanoids, diabetic retinopathy and, axons to optic disc and exit from eye 551–553, 552f 553 and, 383f, 383–385 in humans, 547 Eight-arm radial maze, 18 Ephb4, retinal vascularization and, 288 in mice, 547–548, 548f Electrical stimulation, retinal ganglion cell Ephrin(s), targeting of retinal ganglion cell nonproliferative, mouse models of vascular axon growth and, 404–405 axons to optic disc and exit from eye lesions of, 548–551 Electroporation, 621–631 and, 383f, 383–385 chemically induced diabetes and, controlling expression following, 626–630 Ephrin ligands, retinal vascularization and, 548–549, 549f cell type–specifi c regulation using 288 nondiabetic, developing diabetic-like specifi c promoters and, 626–627, Ephrin-B1/ephrin-B2, retinal ganglion cell retinopathy, 550–551 628t, 628f–630f, 629 axon divergence at chiasm and, 393, spontaneous diabetes and, 549–550 conditional RNAi and, 629–630, 394f, 395 nonproliferative stage of, 547 632f Erythropoietin, proliferative retinopathy and, proliferative, mouse models of, 553–554 temporal and cell type–specifi c 292–293 insulin-like growth factor-1 and, 554 regulation and, 629, 631f Esi-1/Elf3, in cornea and lens development, oxygen-induced retinopathy and, temporal regulation and, 626, 627f 703 553–554 future applications of, 630–631 Ethylnitrosourea (ENU), as mutagenic agent, VEGF overexpression and, 554 method of, 621–626 493 proliferative stage of, 547 in vitro, retinal, 623, 625f, 625–626, plate Evans, Martin J., 35 retinal neurodegeneration and, mouse 55, plate 56 Evolution models for study of, 551 in vivo, comparison to other in vivo gene centrifugal model of, 6, 7f Dickkopf1, eye fi eld formation and, 301 delivery methods, 621 of house mice, 6–8, 7f Diffusers, deprivation myopia from, 82 in vivo, brain, 626 sequential (linear) model of, 6–7, 7f Dopaminergic amacrine cells in vivo, retinal, 621–623, 622f–624f, plate Excitatory postsynaptic potentials (EPSPs), genetic labeling of, 597–598 50, plate 51, plate 52, plate 53, plate in lateral geniculate nucleus, 420, mosaic architecture of, 151–153 54 421f, 422, 424 Dorsal terminal nuclei (DTN), retinal Electroretinogram (ERG) Experience-dependent visual cortical projections to, 41 with cone phototransduction gene plasticity, 465–473 Dorsal visual stream, 373f, 373–374 inactivation, 138, 138f adult ocular dominance plasticity and, Dorsolateral geniculate nucleus (dLGN), functional features of cones and, 138, 472–473, 474f 219–229 138f mechanisms of ocular dominance shift in intrinsic physiology of neurons of, Elevated plus maze, 29 mice and, 468–471 219–221 Elevated zero maze, 29 monocular deprivation in juvenile mice calcium currents and, 220 ELOVL4 gene, age-related eye diseases and, and, 468, 469f, 470f hyperpolarization-activated currents 582, 584–588 stimulus-selective response potentiation and, 221 ELOVL4 mice, 613, 638 and, 471–472, 472f oscillations and, 221 Embryonic stem cells, in vitro generation of visually evoked potential recording potassium currents and, 220–221 retinal ganglion cells from, 329–330 technique and, 466, 467f, 468 sodium currents and, 220, 220t Encephalitis, viral, 509 Experimental autoimmune uveitis (EAU) modulation of retinal signal by, 225–228 Endostatin, anti-angiogenic properties of, associated with anti-tumor response to burst and tonic responses and, 227–228, 610 melanoma antigen, 517 228f Endothelial cells, apoptosis of, oxygen- histology of, plate 39 of intrinsic thalamocortical relay cell induced retinopathy and, 293 in human lymphocyte antigen transgenic physiology, 226–227 Endothelial tip cell guidance, retinal mice, 516 local geniculate inhibition and, vascularization and, 287 induced by active immunization with 225–226, 226f Endotoxin-induced uveitis (EIU), 513–515, retinal antigen, 515, 516t, 517f presynaptic, 225 514f induced by adoptive transfer of antigen- output of, 221–225 histology of, plate 39 specifi c T cells, 515 retinogeniculate inputs and spatial Environmental enrichment induced by injection of antigen-pulsed information and, 221–223, 222f–224f plasticity and, 449–459 dendritic cells, 516

index 741 Experimental autoimmune uveitis Fontana’s spaces, 130 Gaze-shifting movements, 87, 88 (continued) Force-choice apparatus, two-alternative, for GC1−/− mice, as model for Leber congenital in mice expressing a transgenic target visual acuity measurement, 18, 20 amaurosis, 611 antigen in the retina, 515–516 Forced choice discrimination task, for Gdf8/Myostatin, control of retinal progenitor pathogenesis of, critical checkpoints in, measuring visual perception, 109 cell proliferation by, 328 plate 39 Formalin test, 25 Geminin, eye fi eld transcription factor spontaneous, 516–517 Forward genetics approach, 66–67, 67f regulation and, 302 Expressed sequence tags (ESTs), 662–663 Fox, cataracts and, 494 Gene(s). See also specifi c genes ey1 mutation, 269 Foxd1, chiasm patterning and, 396 controlling vision, fi nding, 62–63, 64f, ey2 modifi er genes, 269 FOXE3, in cornea and lens development, 65f Eye, of mouse compared to other 701 epistatic interaction between, 651–653, mammalian species, 35 Foxe3, lens development and, 277 652t Eye fi eld transcription factors (EFTFs), Foxg1, chiasm patterning and, 396 Gene deletion, to defi ne role of cholinergic 299–302 Foxn4, Math5 repression in retinal signaling by starburst amacrine cells, expression in retinal progenitor cells, 299, progenitor cells and, 326 598 302–303 Frs2α, lens development and, 277 Gene expression, 685–694, 686f interaction of, 300 Fungal infections, mouse models of, 508 analysis of regulation of, 300–301 FVB/N strain, 15 correlation of retinal pigment transcription targets of, 301–302 FVB/NJ epithelium gene expression and Eye movements, 87–102 anxiety-related behavior tasks and, 29 retinal vascularization and, 692–693 after-nystagmus and velocity storage auditory evoked brainstem response in, isolation of retinal pigment epithelium integrator and, 94–96, 96f 22 and, 688, 689f, 690f, 690–691 angular vestibulo-ocular refl ex and, avoidance learning in, 28 isolation of retinal vasculature and 88–91, 89f, 90f hearing and visual abilities in, 15t subsequent gene expression studies compensatory, 87, 88 pain sensitivity in, 25 and, 688, 689f, 691–692 adaptive properties of, 96–99, 97t, 98f, pattern discrimination in, 18 study methods for, 686–687 99f visual acuity of, 20 transgenics in, 692 control of, importance of, 87 mutation and effect in, 62t in cornea and lens, 697–706 in foveate and afoveate mammals, 87 FVBS/Ant strain, 15 cornea and lens development and, 697, gaze holding and velocity-to-position 698f neural integrator and, 96 G large scale analyses of, 698–699 gaze-shifting, 87–88 regulation of specifi c genes and, nystagmus and, fast phases of, 99–100, GABAC null mice, refractive errors in, 83 703–705

100f GABACR, inhibition mediated by transcription factors and, 699f, off-vertical axis stimulation and, 93–94, alteration of visually and electrically 699–703, plate 66 94f evoked responses of ON-center degeneration networks by expression optokinetic refl ex and, 91, 91f retinal ganglion cells by, 183–184, profi ling of photoreceptors from rd otolith-ocular refl exes and, 91–93, 92f 184f mice and, 679–680 rapid, saccade-like, 233 control of output of bipolar cell synaptic drug-controlled electrically induced, in mice, 235–238, output by, 182–183 Cre-lox recombinase system for study 237f GABAergic neurons, of superior colliculus, of, 600f, 600–601 measurement of, 233–234, 234f 239 reversible, 601 spontaneous, in mice, 234f, 234–235, GAD67 (Gad)-GFP knock-in mice, expression profi le of mRNA from whole 236f GABAergic neurons in, 239 mouse retinas at different postnatal reasons for studying, 87 Galactose feeding, diabetes and, 550 developmental stages and, plate 65 recordings of, applications of, 100–101 α(1,3)-Galactosyltransferase, cataracts and, inducible, in differentiated Müller glia, visual-vestibulo-ocular refl ex and, 89f, 499 plate 61 89–91, 90f Ganglion cell(s), gap junctions of, 169, 170f, mapping of, for ocular dominance Eyeless. See Pax6 171 plasticity assessment, 442–443 functional role of, 171 in mouse eye, 662 F Ganglion cell layer (GCL), 635, 636f in retinal pigment epithelium GAP-43, retinal ganglion cell axon guidance correlation of retinal pigment Fear conditioning, cued and contextual, through visual pathway and, 392f, epithelium gene expression and 27 393 retinal vascularization and, 692–693 Fetal loss, in Ndph knockout mice, Gap junctions, 165–171 isolation of retinal pigment epithelium 534–535 of amacrine cells, 167 and, 688, 689f, 690f, 690–691 Fgfr signaling, lens development and, of bipolar cells, 167 in retinal vasculature 276–277 transgenic mice to study, 596–597 correlation of retinal pigment Field mice, 5 ganglion cell coupling and, 169, 170f, 171 epithelium gene expression and Filensin, cataracts and, 498–499 functional role of, 171 retinal vascularization and, 692–693 Fixation mechanism, 88 of horizontal cells, 166f, 166–167 isolation of retinal vasculature and Fluorescence resonance energy transfer of photoreceptors, 165–166, 166f subsequent gene expression studies (FRET), 597 in proximal rod pathways, 167–169, 168f and, 688, 689f, 691–692 Fluorescent reporters retinal waves and, 346–347 spatial regulation of, using cell type– under control of Thy-1 promoter, 598 Gaze holding, oculomotor neural integrator specifi c promoters, plate 58 subcellular spatial resolution using, 597 and, 96 Gene expression profi ling, 654–655

742 index Gene targeting methods, 594–595, 595f primary open-angle Hearing, in mice, 15t Gene therapy models of, 489 Hearing ability, measurement of, 20, 22 antiangiogenic, 607 mouse model of, 481–482 Hearing loss, in Ndph knockout mice, neurotrophic factor, 613 retinal ganglion cell death in 533–534 for retinal degeneration, 675 regional patterns of, 485–486, plate 33 Heat shock transcription factors vectors for, 605 soma death and axon degeneration and, cataracts and, 496–497 adenoassociated virus. See 486–487, 487f in cornea and lens development, 702 Adenoassociated virus (AAV) gene treatment of, 644 Hematopoietic stem cells (HSCs), retinal therapy future prospects for new therapies for, vascularization and, 289 Gene transfer methods, 593–594, 594f. See 487–488 Herpes simplex virus (HSV) infections, 505 also Electroporation Glaucomatous optic neuropathy, retinal Herpes stromal keratitis (HSK), 505–506 Genetic modifi ers ganglion cell axon regeneration in, Hes1 as cause of phenotypic variation, 651–653, 409 eye fi eld formation and, 301 652t Gli family, control of retinal progenitor cell retinal development and, 324 retinal degeneration and, 652–653 proliferation by, 329 Hes5, eye fi eld formation and, 301 cloning of, strategies for, 653–655 Glial cell(s), in optic nerve, 201–202 Hind limb denervation, as model of chromosomal localization of modifi ed Glial cell line-derived neurotrophic factor anesthesia dolorosa, 25 traits and, 653–654 (GDNF), 613 Hmgn1, in cornea and lens development, gene expression profi ling and, 654–655 retinal ganglion cell axon growth and, 401 701 haplotype analysis and, 654 Glial fi brillary acidic protein-green Horizontal cells microarray analysis and, 654–655 fl uorescent protein (GFAP-GFP) development of, Rb and, 318 modifi er screens using mutagenesis and, transgenic mice, 287 gap junctions of, 166f, 166–167 655 Glucagon amacrine cells, in mouse versus mosaic architecture of, 148–150, 149f, segregating crosses with multiple strains chicken eye, 82–83 150f and, 654 GluR6, signaling through, 596 Hot-plate test, 24–25 Genetic networks in mouse eye, 667f, Glycine receptor α2, photoreceptor House mice, 5 667–668 development and, 305 Hsf4, cataracts and, 496–497 microarray methods and, 669 Gnao1tm1Lbi mice, control of depolarizing Hspg2, cataracts and, 499–500 Genetic tagging technique, to ablate bipolar mGluR6 signaling cascade in, Human genome, 660 starburst amacrine cells, 598 178–179, 179f Human leukocyte antigen (HLA) transgenic Genomics, glaucoma therapy and, 488 GpnmbR150X, pigmentary glaucoma and, 483 mice, experimental autoimmune GFP, expression in rods, plate 63 Grm6nob4 mice uveitis in, 516 Ggta1, cataracts and, 499 control of depolarizing bipolar mGluR6 Hyperoxia, depletion-induced, lack of Gja3, cataracts and, 495–496 signaling cascade in, 178–179, 179f oxygen supply to outer retina and, Gja8 retinal ganglion cell responses in, 181 565–566 cataracts and, 496, 496f, 588 Grm6Tm1Nak mice Hyperpolarizing bipolar cells (HBCs), 136 mutations of, plate 37 control of depolarizing bipolar mGluR6 synaptic transmission in outer retina and, Glaucoma signaling cascade in, 178–179, 179f 176f, 176–179, 177t future prospects for new therapies for, retinal ganglion cell responses in, 181 Hypopigmented mice, 61 487–488 Growth, of retinal ganglion cell axons. See genomics and proteomics and, 488 Retinal ganglion cells (RGCs), axon I neuroprotection as, 487–488, 488f growth and regeneration of genetic component in, 479 Growth factors. See also specifi c growth factors I-κB-ζ, in cornea and lens development, human clinical research on, pattern lens and, 273 702 electroretinography in, 124 retinal vascularization and, 286–287 I/LnJ mice, auditory evoked brainstem mouse models of, 479–489 Growth of mouse eye, 74 response in, 22 accuracy of intraocular pressure Guidance molecules, retinal vascularization Immunoprecipitation (IP), visual cycle measurements in, 480 and, 288 protein interactions and, 729 advantages of, 479 Impact-rebound (I/R) tonometry, 480 of developmental glaucoma, 483 H Inbred strains experimentally induced glaucoma and, genetic variability in, 668 481 Habituation-discrimination test, 22–23 power of, 668 pattern electroretinogram application Habituation-dishabituation test, 22–23 used for research, 13 in, 122–124, 123f Hamilton Eye Institute Mouse Database on lens, 271–272 of pigmentary glaucoma, 483–485, (HEIMED), 664 Inducible nitric acid synthase (iNOS), 484f BXD Genetic Reference Panel of Mice diabetic retinopathy and, 553 of primary congenital glaucoma, 483 and, 664–665, 666t, 667 Inducible RNAi, in retina, plate 62 of primary open-angle glaucoma, genetic networks in eye and, 667, 667f Infantile neuronal ceroid lipofuscinosis 481–482 quantitative trait locus mapping in, (INCL), gene replacement therapy similarity between mouse and human 668–669, 670 for, 612 structures relevant to, 479–480 Hargreaves test, 24, 25 Infectious eye diseases, 505–509 mutagenesis and new models of, 488–489 Hartmann-Shack aberrometry bacterial, 506–508 neurodegeneration and, 485, 485f optical aberration measurement using, fungal, 508 optic nerve excavation in, prevention by 79f, 79–80 herpetic, 505–506 radiation treatment, plate 35 spherical aberration found on, 75–76 parasitic, 508–509 overview of, 479 Head tilt mice, 101 retinal, mouse models of, 509

index 743 Inferometry, low-coherence, 77–79, 78f diabetes-induced retinal posttranslational modifi cations and, 715 Infrared photoretinoscopy, 74–76, 76f, 77 neurodegeneration in, 551 development of, 267, 268f, 697, 698f Inhibitory postsynaptic potentials (IPSPs), in Knockout mouse models, 65, 635–645. See transcription factors involved in, 699f, lateral geniculate nucleus, 420, 421f also specifi c models 699–703, plate 36 Inner plexiform layer (IPL) anterior chamber cell types and, 644–645 epithelial cells of, 267 dendrites in, 194 developers of, 35 fi ber cells of, 267 lateral inhibition in, 175 for lens research, 273–274 function of, 267–268 Insulin-like growth factor (IGF) P7, plate 42 gene expression in. See Gene expression, cell death and, 336 refractive errors in, 83 in cornea and lens retinal ganglion cell axon growth and, 401 retinal cell types and, 635, 636f, 637 lens transplantation experiments and, Insulin-like growth factor-1 (IGF-1) retinal pigment epithelium and, 637–639, 270 eye fi eld formation and, 301 639f membranes of, mutations affecting, overexpression of, 554 vascular cell types and, 639–643, 641f, 495–496 visual cortical plasticity and, 456 643f morphological descriptors of, 270 Interferometer, Michelson, 79 mutations affecting structural proteins of, Interferon-τ (IFN-τ) L cataracts and, 496–499 experimental autoimmune uveitis and, proteomics of, 711–718, 716f 520 Lac repressor-lac operator system, for study crystallins and, 711–713, 716 Pseudomonas aeruginosa infections and, 507 of retinal ganglion cells, 599 posttranslational modifi cations and, 715 Intergeniculate leafl et (IGL), retinal Lamina cribrosa (LC), in glaucoma, 485–486 refractive power of, 73 projections to, 40, 41 Lamina cribrosa region, of optic nerve, 201, research on development of Interlaminar connections, in superior 202f conditional gene alterations using Cre colliculus, 239, 240f Lang, Richard, 275 recombinase and, 274–275, 275f Interleukin-1β (IL-1β), diabetic retinopathy Lateral geniculate nucleus (LGN) customizing mouse genome for, and, 553 cellular composition of, 419 273–274 Interleukin-8 (IL-8) differentiation of neurons of, 419 differences among mouse strains and, proliferative retinopathy and, 292, 293 dorsal. See Dorsolateral geniculate nucleus 271–272 Pseudomonas aeruginosa infections and, 507 (dLGN) historical background of, 268–269 Interphotoreceptor retinoid-binding protein excitatory responses in, 420, 422, 424 lens complementation system for, 274 (IRBP) eye-specifi c segregation in, development lens fi ber differentiation and, 278 experimental autoimmune uveitis induced of, 415–416, 416f, 417f, 418 molecular biology and, 272 by, 515 inhibitory responses in, 422 mouse and human lenses compared in visual cycle, 726 retinal ganglion cell projections to, 192 and, 270–271 Intracellular adhesion molecule-1 (ICAM-1), synaptic connectivity patterns in, 422, mouse lens induction and, 275–278, diabetic retinopathy and, 553 423f, 424 276f Intraocular pressure (IOP) synaptic remodeling in, 429–430, 430f, murine models for, 269–270 aqueous humor outfl ow and, 131 430–431, 431f nonmurine model systems for, 268–269 measurement of, accuracy of, 480 activity and, 431–432 transgenic mice for, 272–273 Ischemic optic neuropathy, retinal ganglion comparison with remodeling in other structure of, 267 cell axon regeneration in, 409 regions of visual system, 433–434 Lens complementation system, 274 Islet2 cortical critical period in, 433 Leukemia inhibitory factor (LIF), retinal retinal ganglion cell axon divergence at genes involved in, 434–435 vascularization and, 287 chiasm and, 395 plasticity in lateral geniculate nucleus Leukocytes as retinal ganglion cell marker, 193 and, 432–433 adherence in retinal microvasculature of Isoelectric focusing (IEF), in proteomics, superior colliculus and, 433–434 diabetic mouse, plate 47 713–714 vision-sensitive phase of, 433 mouse model of oxygen-induced Isomerohydrolase, in visual cycle, 723–724 Lateral terminal nuclei (LTN), retinal retinopathy and, 293–294 projections to, 41 Lhx2, as eye fi eld transcription factor, 300 J Lateromedial area, extrastriate, intracortical Lid suture, deprivation myopia from, 82 connections of, plate 9, plate 10 Liegéois, Nanette, 274 Jackson Laboratory, 13, 581–582 Lathrop, Abbie, 13 Light Junctional adhesion molecule-B (JAM-B), as Learning tasks, 25–29 acceleration of photoreceptor retinal ganglion cell marker, 193 visually dependent, 25–28 degeneration by, lack of oxygen Juxtacanalicular connective tissue (JCT), visually independent, 28–29 supply to outer retina and, 566 131, 131f Leber congenital amaurosis (LCA), gene continuous, refractive development and, replacement therapy for, 611–612 82 K Lecithin:retinol acyltransferase (LRAT), in raising of oxygen levels in outer retina by, visual cycle, 723 565 Keratins, expression in cornea, 705 Le-Cre strain, Cre expression in, plate 12 responses to exposure to, Rpe65 alleles Keratitis, stromal, herpes, 505–506 Lens, 267–279 and, 650–651 Keratocan, expression in cornea, 705 cell proliferation in, 270 retinal degeneration induced by, 16, 573 Keratomycosis, 508 connexins in, cataracts and, 495–496, mouse strains with, 16 Kessler, Paul Leonhard, 270 496f Light-dark transition test, 29 Kinases, cell death and, 338 crystallins in, 703–704, 704f, 711–713, Lim2, cataracts and, 495 KKAY mouse 716, 716f Lineage tracing, Cre-lox recombinase system diabetes in, 550 posttranslational modifi cation of, 716 for study of, 601

744 index Linear control systems analysis, 88n Maternal care, neuronal and behavioral Hamilton Eye Institute Mouse Database Linear model of evolution, 6–7, 7f development and, 451, 455–456, and, 664 Linear vestibulo-ocular refl ex (lVOR), 88 458 Microarray-based technologies, glaucoma Lip12, cataracts and, 588 Math5 therapy and, 488 Lipofuscin, in retinal pigment epithelium, circadian photoentrainment and, 210, Microglia, mouse model of oxygen-induced 539–544, 540f, 638 211–212 retinopathy and, 293–294 autofl uorescence of, plate 44 regulation of expression of, 325–327 Microphthalmia, in C57BL mice, 271 inhibiting formation of fl uorophores and, of duration of expression, 325–326, Mip, cataracts and, 495 targeting visual cycle for, 543f, 326f MLR10 mice, 274–275 543–544 math5 activation in retinal progenitor Cre expression in, plate 12 Leu450Met variant in murine Rpe65 cells and, 325 MLR39 mice, 275 associated with, 542–543, 543f repressing expression in other retinal Cre expression in, plate 12 Rpe65−/− mice and, 539–540, 540f progenitor cells and, 326–327 MOLF/EiJ strain Stargardt macular degeneration and retinal ganglion cell development and, anxiety-related behavior tasks and, 29 Abca4/Abcr null mutant mice and, 324–325 hearing and visual abilities in, 15t 540–542, 541f activation of retinal ganglion cell fate pattern discrimination in, 18 Liquid chromatography, in proteomics, and, 325 visual acuity of, 20 714 cell cycle progression and, 324 Monocular deprivation (MD) Listeria monocytogenes infections, 508 retinal ganglion cell competence and, in juvenile mice, effects of, 468, 469f, 470f Little, Clarence Cook, 13, 269 324 ocular dominance shift and, 470–471 Long-term depression (LTD) suppression of non-retinal ganglion cell ocular dominance studies and. See Ocular AMPA receptors and, 470 fates and, 324–325 dominance (OD) plasticity aVOR gain and, 100 retinal ganglion cell differentiation M-opsin, cone, expression of, 136, 138–139 ocular dominance shift and, 468 downstream of, regulation of, Morris water maze, 25–26, 26f Long-term potentiation (LTP) 327–329 for measuring visual perception, 109–110 mechanism for, 471 control of retinal progenitor cell Mosaic architecture, of retina, 147–153 ocular dominance shift and, 468 proliferation by retinal ganglion cell- cholinergic amacrine cells and, 150–151, retinoic acid and, 366 secreted signaling molecules and, 151f Lop10, cataracts and, 588 328–329 development of, 147–148, 148f Low-coherence inferometry, 77–79, 78f genes regulated by Pou4f2 and, dopaminergic amacrine cells and, Lrat−/− mice, 723 327–328 151–153 Lucentis (ranibizumab), for age-related regulation of retinal ganglion cell axon horizontal cells and, 148–150, 149f, 150f macular degeneration, 607 outgrowth and pathfi nding and, 328 Mouse genome, 660–662 Lurcher mice, 101 transition for retinal ganglion cell sequence differences among mice and, Lysosomal storage disease, gene replacement competence to retinal ganglion cell 660–662, 661f, 662t therapy for, 612 commitment and, 327 Mouse hepatitis virus (MHV) infections, 509 Math5 Mouse models. See also specifi c models M expression in retinogenesis, plate 16 advantages of, 363 retinal ganglion cell development and, 194 historical background of, 61–62, 62t Mab21/2, lens development and, 277 Matrix metalloproteinase-9 (MMP-9), mutant. See also specifi c models MacDowell, E. Carlton, 13 corneal neovascularization and, 506 eye movements and, 100–101 macrophage inhibitory protein-2 (MIP-2), Mechanical sensitivity, von Frey fi lament test of synaptic transmission in outer retina, herpes simplex virus infection and, of, 24 176f, 176–179, 177t 506 Medial terminal nucleus (MTN), retinal Mox-Cre;RbLox/Lox mice, rod development in, Macrophages, mouse model of oxygen- projections to, 41 314 induced retinopathy and, 294 Melanoma antigen, anti-tumor response to, Mucopolysaccharidosis type VII (MPS VII), Macugen (pegaptanib), for age-related uveitis associated with, 516 gene replacement therapy for, 612 macular degeneration, 607 Melanopsin, 213–214 Müller glia, differentiated, inducible Macular degeneration phototransduction mechanism and, expression in, plate 61 age-related, gene therapy for, 607 213–214 Multielectrode arrays (MEAs), for retinal Stargardt, in Abca4/Abcr null mutant mice, Melanosomes, DBA/2J pigment dispersion wave measurement, 343 540–542, 541f and, plate 32 Murine coronavirus infections, 509 Maf, cataracts and, 494 Membrane currents, in dorsolateral Murine cytomegalovirus infections (MCMV), Maf transcription factors, in cornea and lens geniculate nucleus, 220f, 220–221 509 development, 702 Memory tasks Mus, 3–8 Magnetic search coil oculography, 89 visually dependent, 25–28 phylogenetic relationships in genus, 8 Major histocompatibility complex I (MHC I) visually independent, 28–29 subgenera of, 3–6, 4f antigen, lateral geniculate nucleus Mesencephalon, visual cortex connections Mus booduga, 5, 8 synaptic remodeling and, 434–435 with, 46 Mus caroli, 8 MA/MyJ strain, auditory evoked brainstem Michelson interferometer, 79 Mus cervicolor, 5, 8 response in, 22 Microarray analysis, 654–655, 663–667 Mus Coelomys, 3–5, 8 Mann, Ida, 269 BXD Genetic Reference Panel of Mice Mus cookii, 8 Mass spectrometry and, 664–665, 666t, 667 Mus crociduroides, 5 in proteomics, 714 defi ning genetic networks in, 669 Mus cypriacus, 6 visual cycle protein interactions and, expression profi ling using, 675–676 Mus famulus, 5, 8 729 gene expression and, 686–687 Mus fernandoni, 5

index 745 Mus fragulicauda, 5, 8 protection against, by degradation of hyaloid vessel regression versus Mus lepidoides, 5–6, 8 photoreceptors, 565 angiogenesis of retinal blood vessels Mus macedonicus, 6, 8 Netrin-1 in, 532, 533f Mus mayori, 5 regulation of retinal ganglion cell axon phases of, 532–533 Mus Mus, 3–4, 8 exit from eye by, 383f, 384 retinal physiology of, 530 Mus mus castaneus, 6, 7, 8 retinal ganglion cell axon guidance sprouting angiogenesis failure in, Mus mus domesticus, 6–7, 8 through visual pathway and, 392, 531–532 Mus mus gentilulus, 6, 7, 8 392f molecular basis of, 527–528 Mus mus musticus, 6, 7, 8 NEUBank, 663 NDP gene conservation and expression Mus musculus, 3, 5, 6, 8 Neurodegeneration, glaucoma and, 485, pattern and, 528, 529f evolutionary history of, 6–8, 7f 485f norrin and, 528–529 Mus Nannomys, 3, 5, 8 Neurofi lament H, antibodies against, as transgenic mouse line with norrin Mus nitidulus, 5, 8 retinal ganglion cell marker, 193 overexpression in lens and, 534 Mus pahari, 5 Neuroglobin, retinal oxygen consumption Norrin, 528 Mus phillipsi, 5 and, 562 ectopic expression in lens, rescue of Mus plathythrix, 5 Neuronal plasticity, RALDH3 colocalization knockout phenotype by, 534 Mus Pyromys, 3–4, 5, 8 with markers for, 368, 369f overexpression in lens, transgenic mouse Mus Sensu stricto, 5 Neuronal tissue, in optic nerve, 201 line with, 534 Mus shortridgei, 5 Neuron-specifi c enolase (NSE), cell death Norrin knockout mice, hematoxylin-eosin- Mus spicilegus, 6, 8 and, 337 stained sections of whole eyes from, Mus spretus, 6, 8 Neuropathic pain, measurement, 25 plate 43 Mus terricolor, 8 Neuroprotection, for glaucoma treatment, Notch pathway Mus vulcani, 5 487–488, 488f eye fi eld formation and, 301 Mutagenesis, modifi er screens using, 655 Neurotrophic factor gene therapy, 613 retinogenesis regulation and, 303–304 Mutant mouse models, 14. See also specifi c Neurotrophin(s), cell death and, 336 Npp, 501 models Neurotrophin-3 Nr-CAM, retinal ganglion cell axon eye movements and, 100–101 postnatal cortical maturation patterns divergence at chiasm and, 394f, 395 of synaptic transmission in outer retina, defi ned by, 369–370, 370f Nr2e3, rod development and, 316 176f, 176–179, 177t RALDH3 relationship with, 368–369, Nr2e3, photoreceptor development and, postsynaptic mouse mutants and, 177t, 369f 304–305 178–179, 179f Neutrophils, Pseudomonas aeruginosa infections NRL, gene profi ling of purifi ed presynaptic mouse mutants and, 177t, and, 507 photoreceptors and, 676, 677f 177–178 Nhs1 protein, cataracts and, 499 Nrl, photoreceptor development and, Muthukkaruppan, V., 269–270 Night blindness, stationary, congenital, 304–305 Myelinated portion, of optic nerve, 201, 202f 650 Nrl, rod development and, 316 Myelinogenesis, of optic nerve, 201–202 NMDA, excitatory lateral geniculate nucleus Nrl −/− knockout mice MYO7A, age-related eye diseases and, 584 responses and, 420 as model for central fi eld loss, 613 Myocilin (MYOC), in primary open-angle NMDA receptors (NMDARs), 223–225 photoreceptors of glaucoma, 481–482 ocular dominance shift and, 469 caveats for investigations of, 142 Myopia, deprivation in reticulogeniculate synapses, 431, 439 cones as, 139, 141–144 induced by frosted diffusers, 82 NMDA-type glutamate receptor antagonist, cone-specifi c genes and their molecular from lid suture, 82 stratum griseum intermediale burst function and, 143–144 generation and, 240 differentiation of, 143 N nob knockout mice, refractive errors in, 83 mouse cone protein biochemistry and, NOD strain, diabetes in, 550 144 nAChR subunits, retinal waves and, NOD/LtJ strain, auditory evoked brainstem prospects for studies using, 143–144 345–346 response in, 22 Nuclear posterior polar opacity, 501 Nakano cataract, 501 Noggin, eye fi eld formation and, 301 Nucleus of the optic tract (NOT), retinal Nance-Horan syndrome (NHS), 499 Nonpigmented ciliary epithelium (NPE), 129 projections to, 41 Nbn gene, senile cataracts and, 500 Nop, cataracts and, 497 Null mutation. See Knockout mouse models NDP, 528 NOR/LtJ strain, auditory evoked brainstem Nystagmus evolutionary conservation and expression response in, 22 fast phases of, 99–100, 100f pattern of, 528, 529f Norrie, Gordon, 527 off-vertical axis rotation engendering, 94 Ndph, 529–530 Norrie, function of, 528–529 optokinetic, velocity storage integrator Ndst1, lens development and, 277 Norrie disease, 527–535 and, 95f, 95–96 Negative masking, circadian clinical background of, 527 optokinetic after-nystagmus and, 94 photoentrainment and, 210 extraocular features of, 527 postrotatory, 94 Neo-antigen-driven experimental knockout mouse model for, 529–530 Nyxnob mice autoimmune uveitis, 515–516 abnormal retinal vascular development control of depolarizing bipolar mGluR6 Neovascularization in, 530–531, 531f, 532f signaling cascade in, 178–179, choroidal, gene therapy for, 610 ectopic norrin expression in lens and, 179f corneal, matrix metalloproteinase-9 and, 534 retinal ganglion cell responses in, 181 506 fetal loss in homozygous females and, NZB/BINJ strain, taste ability in, 23 retinal 534–535 NZW strain, mutation and effect in, 62t gene therapy for, 607, 609–610 hearing loss and abnormal cochlear NZW/LacJ strain, photoreceptor response limitation by laser burns, 565 vasculature in, 533–534 damage by light and, 575, 577

746 index O 129S2/Sv strain, anxiety-related behavior traumatic, retinal ganglion cell axon tasks and, 29 regeneration in, 409, 409f ob/ob mice, diabetes in, 550 129/SvEms strain, learning and memory in, Optic vesicle (OV), 267 Ocular dominance (OD), mapping of, plate 26 27 Optical imaging, for ocular dominance Ocular dominance (OD) plasticity, 439–446. 129/SvEvTac strain plasticity assessment, 440f, 440–441, See also Visual cortical plasticity, avoidance learning in, 28 441f experience-dependent pattern discrimination in, 18 Optical interferometry tonometry (OIT), 480 adult, 443, 444f, plate 27 129SvJ. See 129X1/SvJ Optics, of mouse eye, 74 enhancement by prior experience, 445f, 129/SvPasCrl strain, conditioned odor Optineurin (OPTN), primary open-angle 445–446, 446f preference in, 28 glaucoma and, 482 mechanisms of, 443–445 129Sv-ter/C57BL/6 mice, olfactory ability Optokinetic after-nystagmus (OKAN), behavioral correlates of, 447 in, 22, 23 velocity storage integrator and, 95f, chondroitin sulfate proteoglycans and, 129X1/SvJ strain 95–96 454–455 auditory evoked brainstem response in, 22 Optokinetic drum, 20 extended duration visually evoked pain sensitivity in, 25 Optokinetic nystagmus (OKN), velocity potentials for assessment of, plate 31 Open fi eld test, 29 storage integrator and, 95f, 95–96 juvenile, mechanisms of, 443–445 Operant olfactometer, 22, 23 Optokinetic refl ex (OKR), 88, 91, 91f methods for assessing, 439–443 Opn4 −1− mice, circadian photoentrainment adaptation of, 98f, 98–99, 99f calcium imaging with two-photon and, 210, 211 measurement of, 112–113, 114f microscopy as, 441–442, 442f Opsins Optomotor response, “whole body,” spatial mapping of gene expression as, of cones, expression of, 136, 138–139 vision and, 81–82 442–443 development of, 305 Optomotor test apparatus, 17f optical imaging as, 440f, 440–441, 441f signaling molecules responsible for Organelles, loss during lens differentiation, single-unit recordings as, 439 expression of, 304–306 278 visually evoked potentials as, 439–440 Optic chiasm Orienting vestibulo-ocular refl ex, 92 ocular dominance column plasticity and, regulatory genes in retina and chiasm Otolith-ocular refl exes, 91–92, 92f 465–466 important for patterning, 396–397 Outer nuclear layer (ONL), 635, 636f Ocular hypertension, treatment of, 644 retinal ganglion cell axon divergence at, Outer plexiform layer (OPL), 637 Oculography, applications of, 101 393–396 lateral inhibition in, 175 Oculomotor control, importance of, 87 crossed projection and, 395–396 Oxygen, 559–569 Oculomotor neural integrator, 96 uncrossed projection and, 393–395 delivery to retina, 559–561 Odor discrimination ability, measurement of, retinal ganglion cell axon guidance choroidal circulation and, 560–561 22–23 toward, 392f, 392–393 retinal circulation and, 559–560 Odor preference, conditioned, 28 Optic disc inhaled Off-vertical axis rotation (AVOR), 93–94, 94f directed growth of retinal ganglion cell blocking of vasogenesis by, 563 Olfactory ability, measurement of, 22–23 axons toward, 382–384, 383f killing of photoreceptors by, 562–563, Olfactory tubing maze, 28 targeting of retinal ganglion cell axons to, 564f, plate 48 Oligodendrocytes, in optic nerve, 202 383f, 383–384 lack of oxygen supply to outer retina Olivary pretectal nuclei (OPT), retinal Optic disc astrocyte precursor cells (ODAPs), and, 562–563, 563f projections to, 41 390, 390f lack of supply to outer retina, 562–568 ON and OFF pathways in mouse retina, Optic fi ber layer (OFL) acceleration of photoreceptor 353–360 control of initial retinal ganglion cell axon degeneration by light and, 566 cellular and synaptic structure of, outgrowth polarity in, 381–382, 382f degeneration of edge of normal retina 353–354, 354f retinal ganglion cell axon restriction to, and, 566–568, 567f segregation of 379–381, 380f depletion-induced hyperoxia and, mechanisms of, 358–360, 359f, 360f Optic nerve, 201–204 565–566 retinal synaptic circuitry development astrocytes and astrocyte progenitors in, inhaled oxygen and, 562–563, 563f and, 354–357, 355f, 356f 390, 390f reduction in photoreceptor metabolism synaptic activity and, 357–358 connective tissue in, 203, 203f and, 564–565 Onchocerca volvulus infections, 508 development of, 201–202 retinal detachment and, 564 129/J. See 129P3/J strain glaucomatous excavation of, prevention oxygen stress during development and, 129P3/J strain by radiation treatment, plate 35 568, plate 49 auditory evoked brainstem response in, 22 morphological features of, 201, 202f retinal consumption of, 561–562 mutation and effect in, 62t neuronal and glial tissue in, 202–203, in adults, 561f, 561–562 129P3/PJ, mutation and effect in, 62t 203f developmental onset of, 562 pain sensitivity in, 25 retinal ganglion cell axon projection neuroglobin and, 562 tactile sensitivity in, 24 through, 391–392, 392f retinal degeneration and, 568–569 129/ReJ strain, auditory evoked brainstem vascular supply of, 203–204, 204f Oxygen-induced retinopathy (OIR), 285, response in, 22 Optic nerve head, 201, 202f 553–554 129S1/SvImJ strain Optic neuritis, retinal ganglion cell axon epithelial cell death and, 293 hearing and visual abilities in, 15t regeneration in, 409 mouse model of, 289–294. See also 129/S1, olfactory ability in, 22, 23 Optic neuropathy Retinopathy, of prematurity (ROP) pattern discrimination in, 18 glaucomatous, retinal ganglion cell axon characterization of, 289–291, 291f, 292f photoreceptor response damage by light regeneration in, 409 cytokines and, 292–293 and, 575, 577 ischemic, retinal ganglion cell axon endothelial cell apoptosis and, 293 visual acuity of, 20 regeneration in, 409 microglia and leukocytes and, 293–294

index 747 Oxygen-induced retinopathy (continued) Pericyte(s), retinal vascularization and, 288, Pigment dispersion syndrome (PDS), retinal fl at-mount preparation from, 290–291 483–485, 484f plate 13 Pericyte recruitment, 642 Pineal melatonin rhythm, circadian VEGF-A and, 291–292 Pericyte-derived angiopoietin-1, retinal photoentrainment and, 210 vascularization and, 288 Pitx2, in cornea and lens development, 701 P Perlecan, cataracts and, 499–500 Pitx3, cataracts and, 493–494, 494f Phakinin, cataracts and, 498 Pitx3, in cornea and lens development, 701 P7 knockout mice, plate 42 Phenotypic variation Placental growth factor (PGF), retinal P7 wild type mice, plate 42 alleles as cause of, 649–651 vascularization and, 286–287 P21 knockout mice, central retina from, genetic modifi ers as cause of, 651–653, Plasmids, delivery using electroporation. See plate 41 652t Electroporation P21 wild type mice, central retina from, retinal degeneration and, 652–653 Plasminogen activator inhibitor-1 (PAI-1), plate 41 Photokeratometry, 76–77, 78f diabetes and, 550–551 p107 Photoreceptors, 635, 636f, 637. See also Plasticity retinal development and, 313 Cone(s); Rod(s) environmental enrichment and. See Visual rod development and, 316 candidates for light damage quantitative cortical plasticity p130, retinal development and, 313 trait loci and, 577–579, 578t in lateral geniculate nucleus, mouse Pac1r, circadian photoentrainment and, cell death of, pathways of, 678–679, 679f compared to other species and, 214 Cx36 expression by, plate 5 432–433 Pain sensitivity, measurement of, 24–25 degeneration of ocular dominance. See Ocular dominance Paramedian pontine reticular formation by light, 566 (OD) plasticity (PPRF), 238 Pde6b mutations leading to, 650 reticulogeniculate synapses remodeling Parasitic infections, 508–509 Rpe65 alleles and, 650–651 and, 431–432 Pars plicata region, 129 Rpgrip 1 mutations leading to, 650 Platelet-derived growth factor-A (PDGF-A), Pathogen-associated molecular patterns degradation of, protection against retinal retinal vascularization and, 287 (PAMPs), 519 neovascularization by, 565 Platelet-derived growth factor-B (PDGF-B) Pattern electroretinogram (PERG), retinal depletion of, raising of oxygen levels in diabetes and, 551 ganglion cell activity measurement outer retina by, 565 retinal vascularization and, 288 by, 119–124, 120f development of, 304–306 Postrotatory nystagmus (PRN), 94 correlates of visual behaviors and, biological network characteristics and Posttranslational modifi cations, of proteins, 120–121, 121f relevance to photoreceptors and, 715 in human clinical research, 124 676–677 Potassium currents, in dorsolateral geniculate limitations of, 124 critical period in, 568 nucleus, 220–221 methods for, 120 hierarchy in regulatory networks POU homeodomain transcription factors, in in mouse models of glaucoma, 122–124, underlying photoreceptor cornea and lens development, 701 123f development and, 677–678, 678f POU4f1, retinal ganglion cell development in study of central nervous system NRL and gene profi ling of purifi ed and, 194 plasticity and degeneration, 121–122 photoreceptors and, 676, 677f Pou4f2 Pax6 expression profi ling of, degeneration expression in retinogenesis, plate 16 in cornea and lens development, 699–700 networks and, 679–680 genes regulated by, 327–328 eye fi eld formation and, 301 gap junctions of, 165–166, 166f POU4f2, retinal ganglion cell development Notch1 retinal development and, 323–324 killing of, by inhaled oxygen, 562–563, and, 194 Pax6 564f, plate 48 POU4f3, retinal ganglion cell development cataracts and, 493 by light damage of, 566 and, 194 as eye fi eld transcription factor, 299 light damage of, 573–579 PPT1, 612 Le-Cre mice and, 274 gene modifi er having strong infl uence P/Q mutants, 101 lens development and, 275–277, 276f on, 573–575, 576f, 577, 577f Presumptive lens ectoderm (PLE), 267 retinal ganglion cell development and, of mouse compared to other mammalian Primary congenital glaucoma (PCG), 483 194 species, 36 Primary open-angle glaucoma (POAG) retinal development and, 322–323 at peripheral margin of retina, stress from models of, 489 Pax6αCre line, 598 early postnatal life and, plate 49 mouse model of, 481–482 Pax6-Cre;RbLox/Lox mice, rod development in, phagocytosis of outer segments of, 638 Prior experience, enhancement of ocular 314, 315 promoter transgenes and, 595 dominance plasticity by, 445f, Pde6b, age-related eye diseases and, 584 reduction in metabolism of, lack of 445–446, 446f Pde6b gene, 14, 63 oxygen supply to outer retina and, Promoter transgenes, and photoreceptors, rd mutation of, 61 564–565 595 rd1 mutation of, 26 retinal pigment epithelium relationship Prostaglandin analogues, for intraocular Pdeb6b mutations, 650 with, 639 hypertension and glaucoma, 644 Pde6brd1 mutation, 271 targeted ablation to assess role of, Protein(s). See also specifi c proteins Pearlman, Alan, 245 595–596 posttranslational modifi cations of, 715 PEDF, in gene therapy for retinal toxicity of depletion-induced hyperoxia to, proteome-wide identifi cation of species of, neovascularization, 607, 609 565–566 715 Pentraxins, lateral geniculate nucleus Photoretinoscopy, infrared, 74–76, 76f, 77 Rb family of, retinal development and, synaptic remodeling and, 435 Photosensitivity, circadian, 209 311–319 Per genes, circadian photoentrainment and, Physical contact, plasticity and, 455f, intrinsic genetic compensation and 214, 214f 455–456 redundancy and, 312f, 312–313

748 index Protein(s) (continued) Refractive errors physiology of, in norrin knockout mice, rod development and, 216f, 313–317, induction of, by frosted diffusers or 530 315f spectacle lenses, 82–83 retinal ganglion cell axon exit from, species-specifi c differences in Rb family in knockout mouse models, 83 391 compensation and, 313 Regeneration, of retinal ganglion cell axons. vascular development of, in norrin synaptogenesis defects in Rb-defi cient See Retinal ganglion cells (RGCs), knockout mice, 530–531, 531f, retinas and, 317–318, 318f axon growth and regeneration of 532f Protein-bound carbohydrates, cataracts and, Regulatory networks whole mount, confocal image of, plate 4 499–500 degeneration and, expression profi ling of Retinal antigen, experimental autoimmune Proteomics photoreceptors from rd mice and, uveitis induced by, 515, 516t, 517f defi nition of, 711 679–680 Retinal circulation, oxygen delivery to retina glaucoma therapy and, 488 model for retinal ganglion cell and, 559–560 of lens, 711–718 development, plate 15 Retinal degeneration, 675–680 of visual cycle, 727–729 photoreceptors and, 676–677 age-related, in human and mouse eyes, of interacting components, 727–729 underlying photoreceptor development, 582, 584–588 Prox1, lens fi ber differentiation and, 278 hierarchy in, 677–678, 678f expression profi ling of photoreceptors Prox1, in cornea and lens development, Reinforcement-based tasks, for measuring from rd mice and, 679–680 700–701 visual perception, 109–111, expression profi ling using microarrays Prph2Rd2/Rd2 mouse, gene replacement therapy 111f–113f and, 575–676 for, for retinal degeneration in, Reticulogeniculate synapses. See Lateral gene replacement therapy for, 610–611 610–611 geniculate nucleus (LGN), synaptic gene therapy for, 675 prRdh−/− mice, 723 remodeling in genetic modifi cation of, 652–653 Pseudomonas aeruginosa infections, 506–507, Retina light-induced, 16 508 cell types in, 635, 636f, 637 mouse strains with, 16 Ptf1a, Math5 repression in retinal progenitor developing, plate 14 mouse models of, 678–679, 679f cells and, 326–327 electroporation and. See Electroporation synaptic reorganization due to, 317–318 Purkinje cell degeneration mice, 101 gap junctions in. See Gap junctions Retinal detachment inducible RNAi in, plate 62 lack of oxygen supply to outer retina and, Q layers of, plate 64 564 lineage tracing in, using cell type–specifi c retinopathy of, oxygen to relieve, 564 Quantitative trait genes (QTGs), for light promoters, plate 60 Retinal G protein-coupled receptor (RGR), damage, 577–579, 578t mature, plate 14 in visual cycle, 724–725 Quantitative trait locus (QTL) analysis, 63, mosaic architecture of, 147–153 Retinal ganglion cells (RGCs) 64f, 65f cholinergic amacrine cells and, activation of, Math5 and, 325 Quantitative trait locus (QTL) mapping, 150–151, 151f axon growth and regeneration of, 668–669, 670 development of, 147–148, 148f 401–410 dopaminergic amacrine cells and, area of action of extracellular signals R 151–153 and, 402–403, 403f horizontal cells and, 148–150, 149f, control of neuronal responsiveness to Radial arm maze, 26–27 150f trophic peptides and, 404f, 404–405 Radial glia, midline, in retinal ganglion cell of mouse compared to other mammalian dendrite growth ability and, 406–407, axon projection pathway, 390–391 species, 35–39 407f Rafferty, Nancy, 270 multicolor labeling of, using cell type– developmental regulation of intrinsic RALDH3 band, medial, anatomical specifi c promoters, plate 59 growth and, 405–406, 406f locations of, plate 20 normal, degeneration of edge of, lack of extracellular signals inducing growth Ramón y Cajal, S., 635 oxygen supply to outer retina and, and, 401–402, 402t Rapid eye movements, saccade-like, 233 566–568, 567f glaucoma and, 486–487, 487f electrically induced, in mice, 235–238, outer, lack of oxygen supply to, 562–568 intrinsic and extrinsic control of 237f acceleration of photoreceptor regeneration and, 409–410 measurement of, 233–234, 234f degeneration by light and, 566 mechanism of axon induction by spontaneous, in mice, 234f, 234–235, 236f degeneration of edge of normal retina extracellular signals and, 403–404 Rb family of proteins, retinal development and, 566–568, 567f molecular changes underlying and, 311–319 depletion-induced hyperoxia and, developmental loss in rapid axon intrinsic genetic compensation and 565–566 growth ability and, 407–408 redundancy and, 312f, 312–313 inhaled oxygen and, 562–563, 563f need for specifi c extrinsic signals for rod development and, 216f, 313–317, reduction in photoreceptor metabolism growth and, 401, 402f 315f and, 564–565 regeneration in mature visual system, species-specifi c differences in Rb family retinal detachment and, 564 408–409 compensation and, 313 outer, raising of oxygen levels in, by light, regulation of, 409–410 synaptogenesis defects in Rb-defi cient 565 study of, 409, 409f retinas and, 317–318, 318f oxygen consumption of, 561–562 study of regeneration and, 409, 409f RBP receptor, in visual cycle, 725 in adults, 561f, 561–562 axon outgrowth and pathfi nding and, RDH5 gene, 725 developmental onset of, 562 379–386, 380f RDH12 mutations, 723 neuroglobin and, 562 control of initial polarity of outgrowth Receptive fi elds (RFs), of dorsolateral oxygen delivery to, 559–561 within optic fi ber layer and, 381–382, geniculate nucleus cells, 221–224, 223f retinal circulation and, 559–560 382f

index 749 Retinal ganglion cells (continued) morphological properties of, plate 6 Retinal pigment epithelium (RPE), 637–639, directed growth toward optic disc, development of, 194, 195f, 196f 639f, plate 64 382–383, 383f of mouse compared to other mammalian function of, 638 dorsal-ventral differences in species, 35, 37–38 gene expression in mechanisms regulating, 385–386 ON and OFF pathway segregation and, correlation of retinal pigment growth cones and guidance cues and, 353–354, 355–360 epithelium gene expression and 379, plate 21 mechanisms of, 358–360, 359f, 360f retinal vascularization and, 692–693 regulation of, 328 retinal synaptic circuitry development isolation of retinal pigment epithelium restriction of axons to optic fi ber layer and, 354–357, 355f, 356f and, 688, 689f, 690f, 690–691 and, 379–381, 380f synaptic activity and, 357–358 lipofuscin of, 539–544, 540f, 638 targeting to optic disc and exit from synaptic circuitry development and, autofl uorescence of, plate 44 eye, 383f, 383–385 355f, 355–357, 356f inhibiting formation of fl uorophores axonal exit from retina and, 391 ON-center, alteration of visually and and, targeting visual cycle for, 543f, cell death of, 333, 334 electrically evoked responses of, by 543–544

in glaucoma, 479, 481, 485–487, 487f, GABACR-mediated feedback Leu450Met variant in murine Rpe65 plate 33, plate 34 inhibition, 183–184, 184f associated with, 542–543, 543f matching sizes of interconnected pattern electroretinogram measurement of Rpe65−/− mice and, 539–540, 540f neuronal populations and, 335, function of, 119–124, 120f Stargardt macular degeneration and 335f correlates of visual behaviors and, Abca4/Abcr null mutant mice and, molecules involved in signaling, 120–121, 121f 540–542, 541f regulating, and executing, 337, 338 in human clinical research, 124 relationship with photoreceptors, 639 neurotrophic hypothesis of, 336 limitations of, 124 visual cycle and, 721–722 classes of, distinguishing, 189–190, 190f, methods for, 120 Retinal progenitor cells (RPCs) 191f, 192 in mouse models of glaucoma, 122–124, differentiation of, 302 competence of, Math5 and, 324 123f eye ﬁ eld transcription factor expression in, crush injury of, plate 23 in study of central nervous system 299, 302–303 dendrites of, growth ability of, axon plasticity and degeneration, 121–122 Math5 activation in, 325 growth ability and, 406–407, 407f phenotypes of, complex, altered outer Math5 repression in, 326–327 development of, 321–330, 322f retinal neurotransmission resulting in, proliferation of developmental regulation of retinal 179 control by retinal ganglion cell-secreted ganglion cell subtypes and, 329 “pioneer axons” of, 389 signaling molecules, 328–329 early regulatory events in, 322–324 projections of, 192, plate 6 regulation of, 311 gene regulatory network for, 321–322, albinism and, 397 Retinal projections, ipsilateral and 323f axon divergence at chiasm and, contralateral, plate 1 Math5 and, 324–325 393–396 Retinal synaptic transmission, 175–184, regulation of Math5 expression and, early development of, 389, 390f 176f 325–327 glia in projection pathway and, control of synaptic output of bipolar cells

regulation of retinal ganglion cell 390–391 by GABACR-mediated inhibition differentiation downstream of Math5 guidance cues and, 391f, 391–393, plate and, 182–183 and, 327–329 21 evoked response alteration of ON-center

in vitro generation of retinal ganglion late phase of development of, 390, 390f retinal ganglion cells by GABACR- cells from embryonic stem cells and, middle phase of development of, mediated inhibition and, 183–184, 329–330 389–390, 390f 184f developmental timing and, 261 new approaches for study of, 397, 398f in outer retina, 175–179 differentiation of, downstream of Math5, regulatory genes in retina and chiasm altered, complex retinal ganglion cell regulation of, 327–329 important for chiasm patterning and, phenotypes resulting from, 179 direction-selective 396–397 postsynaptic mutants and, 177t, calcium imaging of responses of, 598 techniques for studying, plate 22 178–179, 179f genetic tagging to study responses of, retinal waves and. See Retinal waves presynaptic mutants and, 177t, 598 spontaneous burst activities of. See Retinal 177–178 functional properties of, 192 waves retinal ganglion cell responses in mutants development of, 194–197 subtypes of, developmental regulation of, with outer plexiform layer generation and differentiation of, 193–194 329 presynaptic defects and, 179–181, generation from embryonic stem cells, in survival after lesion, 122, 123f 180f vitro, 329–330 YFP expression, dendritic ramiﬁ cation retinal ganglion cell responses in mutants genetic approaches for study of, 599 patterns of, plate 19 with postsynaptic defects in intrinsically photosensitive, 192, 211–212 Retinal infections, mouse models of, 509 depolarizing bipolar cell signaling morphology, ontogeny, and functional Retinal neovascularization and, 181 diversity of, 211–212, 212f Bcl-2 and, 293 Retinal vasculature, plate 45 phototransduction mechanism and, gene therapy for, 607, 609–610 degenerate capillaries in, plate 46 213–214 limitation by laser burns, 565 development of, 285–289, 286f, 289f target brain regions innervated by, protection against, by degradation of gene expression in 212f, 212–213 photoreceptors, 565 correlation of retinal pigment melanopsin-expressing, circadian Retinal network, of mouse compared to epithelium gene expression and photoentrainment and, 210–211 other mammalian species, 36f, retinal vascularization and, molecular markers for, 192–193 36–37 692–693

750 index Retinal vasculature (continued) dorsal visual stream and, 373f, 373–374 Rpe65−/− mice, retinal pigment epithelium isolation of retinal vasculature and photoreceptor development and, 304, 305 lipofuscin in, 539–540, 540f subsequent gene expression studies RALDH2 and, 367, 367f Rpgrip knockout mice, as model for Leber and, 688, 689f, 691–692 RALDH3 and, 367, 368f congenital amaurosis, 612 leukocyte adherence in retinal colocalization with markers for Rpgrip 1 mutations, 650 microvasculature of diabetic mouse neuronal plasticity, 368, 369f RPR65, 637 and, plate 47 maturation patterns in postnatal cortex isomerohydrolase reaction and, 723–724 Retinal waves, 343–348 defi ned by, 369–370, 370f Rupture of lens cataract, 501 cellular mechanisms underlying, retinal relationship between neurotrophin-3 Rx, as eye fi eld transcription factor, 299–300 development and, 343–344, 344f and, 368–369, 369f Rx-Cre transgenic mice, 274 circuits generating, functional stages of, reporter mice and, 365f, 365–366 RXR-τ, opsins and, 305 plate 17 retinoid system and, 364 Rx/rax homeobox transcription factor, 269 gap junctions and, 346–347 Retinoid fl ow in visual cycle, in visual cycle, measurement techniques for, 343 726–727 S mediation of, 357 11-cis-Retinol dehydrogenase, in visual cycle, stage I, properties of, 347, plate 18 725 Saccade(s), 87, 88, 99 stage II Retinol-binding protein, in visual cycle, 725 Saccade-like rapid eye movements mechanisms of, 345f, 345–346 Retinopathy (SLREMs), 233 properties of, plate 18 of detachment, oxygen to relieve, 564 electrically induced, in mice, 235–238, spatiotemporal properties of, 344–345, diabetic. See Diabetic retinopathy 237f 345f oxygen-induced, 553–554 measurement of, 233–234, 234f stage III, properties of, 347 of prematurity (ROP), 285–294, 642 spontaneous, in mice, 234f, 234–235, 236f visual circuit development and, 348, 349f mouse model for study of, 285, 289 Saccadic eye movements, 233–242 Retinaldehyde, 364 scoring system for, 291 study methods for, 233 Retinaldehyde dehydrogenases (RALDHs), 364 Retinopathy scoring system, 291 superior colliculus and, 233. See also RALDH2, 367, 367f Retinorecipient nuclei, of mouse compared Superior colliculus (SC) RALDH3, 367, 368f to other mammalian species, 40–45 SB strain, mutation and effect in, 62t colocalization with markers for Retinoscopy, streak, 75 Scaling, of eye and cortex, 263–264 neuronal plasticity, 368, 369f RF/J strain, hearing and visual abilities in, 16 Schematic eye modeling, 73–74, 74f maturation patterns in postnatal cortex Rgr−/− mice, 724, 725 Schlemm’s canal defi ned by, 369–370, 370f Rhodopsin gene, 63 aqueous humor outfl ow and, 131 relationship between neurotrophin-3 Rhodopsin gene mutations, 651 inner wall cells of, 132, 132f and, 368–369, 369f RIIIS/J strain, tactile sensitivity in, 24 Scotopic signal transmission, of mouse retinoic acid colocalization with sites of Rlbp−/− mice, 726 compared to other mammalian expression of, 365f, 365–366 RNAi, inducible, in retina, plate 62 species, 36f, 36–37 Retinitis, viral, 509 Rod(s). See also Photoreceptors Scotopic threshold response (STR), pattern Retinoblastoma bipolar cells of, ON and OFF pathway electroretinography and, 124 human susceptibility to, 311, 313 segregation and, 354 Second messengers, retinal ganglion cell species-specifi c differences in susceptibility development of, Rb and, 313–317, 315f, axon growth ability and, 408 to, 313 316f Self-complementary AAV vectors (scAAV), Retinofugal projections, of mouse compared dysfunction of, cone damage due to, 566 613–614 to other mammalian species, 39t, gap junctions of, 167 Senescence-accelerated mouse (SAM), 500 39–40, 40f, 41f GFP expression in, plate 63 Senile cataracts, mouse models for, 500 Retinogenesis, early regulatory events in, of mouse compared to other mammalian Sequential model of evolution, 6–7, 7f 322–324 species, 36 Serial analysis of gene expression (SAGE), Retinogeniculate pathway. See also Lateral scaling of, 263 662, 663, 687 geniculate nucleus (LGN) spatial vision and, 81–82 Severe combined immunodefi ciency (SCID), axon segregation in, in developing mouse, Rod monochromatism, gene replacement 506 plate 24 therapy for, 612–613 Shh, control of retinal progenitor cell development of, 415–426, 425f Rod pathways, proximal, gap junctions in, proliferation by, 328 functional composition of developing 167–169, 168f SHIRPA test battery, 30 pathway and, 419–420, 421f, 422 Rod visual cycle. See Visual cycle, rod Shrew mice, 3–5, 8 mechanisms underlying remodeling of Roscoe B. Jackson Memorial Laboratory, Single-cell recordings, cones and, 139, connections and, 424 13 140f–142f structural composition of developing Rpe65, Leu450Met variant in, reduced Single-unit recordings, for ocular dominance pathway and, 418–419 levels of retinal pigment epithelial plasticity assessment, 439 Retinohypothalamic tract (RHT), circadian lipofuscin associated with, 542–543, Sinusoidal stimuli, optokinetic refl ex gain in photoentrainment and, 209–210 543f response to, 91 Retinoic acid (RA), 363–374 Rpe65, photoreceptor response to light and, Sip 1, lens development and, 277 actions in brain, 364–365 574–575 Sip1, in cornea and lens development, 701 data bank searches and, 370–372 RPE65 alleles, 638–639, 639f Site-specifi c recombination, Cre-lox Allen Brain Atlas, 370–371, 371f Rpe65 alleles, retinal responses to light recombinase system for study of, Brain Gene Expression Map, 370 exposure and, 650–651 599–600 evaluation of, 372 Rpe65 knockout mice, as model for Leber Six3, in cornea and lens development, 700 dorsal telencephalon function and, congenital amaurosis, 611–612 Six homeodomain genes, as eye fi eld 366–367 Rpe65−/− mice, photosensitivity in, 214 transcription factors, 300

index 751 SJL/J strain Spatial vision neuromodulator actions and, 241–242 anxiety-related behavior tasks and, 29 illuminances and, 81, 81f retinal projections to, 42f, 42–44, 43f conditioned taste aversion in, 29 rods and cones and, 81–82 Superoxide dismutase, diabetic retinopathy cued and contextual fear conditioning in, Spectacle lenses, refractive errors induced and, 553 27 by, 82 Suprachiasmatic nucleus (SCN) hearing and visual abilities in, 15t, 16 Spemann, Hans, 268 circadian photoentrainment and, mutation and effect in, 62t Spiny mice, 3–4, 5, 8 209–210, 211, 212f, 212–213 pattern discrimination in, 18 Sp1/Krüppel-like transcription factors, in retinal projections to, 40, 41, 212f, visual acuity of, 20 cornea and lens development, 702 212–213 SKH2/J strain, auditory evoked brainstem Spontaneous activity, developmental, SvEvTac. See 129/SvEvTac strain response in, 22 postnatal retinal ganglion cell SWR/J strain, hearing and visual abilities in, Slit1, retinal ganglion cell axon guidance development and, 121–122, 122f 16 through visual pathway and, 392f, SPRET/EiJ strain Synaptic circuitry, retinal, development of, 392–393 hearing and visual abilities in, 15t ON and OFF pathway segregation Slit2, retinal ganglion cell axon guidance pattern discrimination in, 18 and, 354–357, 355f, 356f toward optic chiasm and, 392f, visual acuity of, 20 Synaptic remodeling, 429–435 392–393 Staggerer mutant mice, olfactory ability in, description of, 429 Slit signaling, control of initial retinal 22, 23 in lateral geniculate nucleus, 430f, ganglion cell axon outgrowth polarity Staphylococcus aureus infections, 507–508 430–431, 431f in, 381–382, 382f Starburst amacrine cells (SACs) activity and, 431–432 Small eye artifact, 74 retinal waves and, 346 comparison with remodeling in other Smithies, Oliver, 35 study approaches for, 598 regions of visual system, 433–434 SM/J strain Stargardt disease, 582, 723 genes involved in, 434–435 pattern discrimination in, 18 in Abca4/Abcr null mutant mice, 540–542, plasticity in lateral geniculate nucleus tactile sensitivity in, 24 541f and, 432–433 taste ability in, 23 Stimulation. See also Environmental lateral geniculate nucleus synapses and, visual acuity of, 20 enrichment 429–430 Smooth pursuit movements, 87, 88 early-life, neuronal and behavioral Synaptic transmission, retinal. See Retinal Snell, George D., 13 development and, 450–451 synaptic transmission Sodium currents, in dorsolateral geniculate electrical, retinal ganglion cell axon Synaptogenesis, defects in Rb-defi cient nucleus, 220, 220f growth and, 404–405 retinas, 317–318, 318f Sodium dodecyl sulfate polyacrylamide gel tactile, plasticity and, 455, 456 electrophoresis (SDS-PAGE), in Stimulus-selective response potentiation T proteomics, 713–714 (SRP), 471–472, 472f, 473 Sonic hedgehog. See also Shh Strain background, 65 T cells directed growth of retinal ganglion Stratifi cation patterns, Cre-lox recombinase antigen-specifi c cell axons toward optic disc and, system for study of, 601 experimental autoimmune uveitis 383 Stratum album intermediale (SAI), 235 induced by adoptive transfer of, eye fi eld formation and, 301 Stratum album profundum (SAP), 235 515 optic nerve development and, 201 Stratum griseum intermediale (SGI), 235 migration to eye, 521 S-opsin, cone, expression of, 136, 138–139 burst generation in, 240–241, 241f defects in selection of repertoire of, Sorsby’s fundus dystrophy, gene therapy for, cholinergic innervation of, 242 susceptibility to experimental 609–610 Stratum griseum profundum (SGP), 235 autoimmune uveitis and, 518 Sox, cataracts and, 494 Stratum griseum superfi ciale (SGS), 43, defi cient peripheral tolerance and, Sox1, lens fi ber differentiation and, 278 235 susceptibility to experimental Sox1, in cornea and lens development, Stratum opticum (SO), 43, 235 autoimmune uveitis and, 518–519 701 Stratum zonale (SZ), 235 Pseudomonas aeruginosa infections and, 507 Sox2 Streak infrared, 75 Tactile sensitivity, measurement, 24 in cornea and lens development, 701 Streak retinoscopy, 75 Tactile stimulation, plasticity and, 455, lens development and, 276 Streptozotocin, diabetes induced by, 456 Spacing rule, in horizontal cell mosaic, 548–549, 549f Tail fl ick test, 24 148–150, 149f, 150f Strong, Leonell C., 13 TALE homeobox proteins, eye fi eld Spatial acuity, primary visual cortex and, Sugar-induced cataracts, in mouse, 499 transcription factor regulation by, 51–52 Sulik, Kathleen, 270 301 Spatial frequency (SF) threshold, of Superior colliculus (SC), 233 Targeted ablation, to assess role of optokinetic refl ex, measurement of, electrically induced saccade-like rapid eye photoreceptors, 595–596 113–115, 114f, 115f movements and, 235–238, 237f Targeted gene manipulations, 594–595, Spatial information, retinogeniculate inputs lateral geniculate nucleus synaptic 595f and, 221–223, 222f–224f remodeling and, 433–434 Targeted mutagenesis, 63, 65–66 Spatial regulation, of gene expression, layers of, 235 Taste ability, measurement of, 23–24 using cell type–specifi c promoters, local circuits of, 238–242 Taste aversion, conditioned, 28–29 plate 58 burst generation mechanism and, Tau-lacZ reporter, for study of retinal Spatial resolution 239–241, 241f ganglion cells, 599 of mouse compared to other mammalian cellular properties of, 238, 238f Taurine, photoreceptor development and, species, 38–39 GABAergic, 239 304, 305 in mouse eye, 73 interlaminar connections and, 239, 240f Tcm mutant, 501

752 index Telencephalon, dorsal, retinoic acid and, Transgenic mice, 14–15. See also specifi c pathogenic effectors and, 520 366–367 transgenic mice T cell repertoire selection and, 518 Temporal information, retinogeniculate in gene expression analysis, 692 Uveoscleral outfl ow pathways, 132–133 inputs and, 223–225 for lens research, 272–273 Temporal resolution, primary visual cortex location of transgene, 65–66 V and, 51–52 study of amacrine cells using, 597–598 Tetrodotoxin (TTX), lateral geniculate study of role of gap junctions in bipolar Vacuolated lens mutant, 500 nucleus synaptic remodeling and, 434 cells using, 596–597 V-amacrine cells, 597 Th1, experimental autoimmune uveitis and, temporal control of gene expression in, Vascular cell types, 639–643, 641f, 643f 520 Cre recombinases for, 626, 627f, Vascular endothelial growth factor (VEGF) Th17, experimental autoimmune uveitis plate 57 gene therapy for retinal neovascularization and, 520 uses of, 65 and, 609 Thalamocortical relay cells (TCs) Translational vestibulo-ocular refl ex herpes simplex virus infection and, 506 calcium current of, 220 (transVOR), 92 overexpression of, diabetic retinopathy hyperpolarization-activated currents of, Traumatic optic neuropathy, retinal and, 554 221 ganglion cell axon regeneration in, Vascular endothelial growth factor-A intrinsic conductances of, modulation of, 409, 409f (VEGF-A) 226–227 Tα1–3RT τTG mice, olfactory ability in, in angiogenesis, 640–641 potassium current of, 220–221 22, 23 oxygen-induced retinopathy and, 290, Thalamus, dorsal and ventral, visual cortex Two-bottle test, of taste ability, 23–24 291–292 connections with, 46 Two-dimensional electrophoresis, in retinal vascularization and, 286, 287 Thanatins, cell death and, 337 proteomics, 714–715 Vascular patterning, 642 Thermal nociception, measurement of, Tyrosine hydroxylase (TH), primary Vascularization, 640, 641f 24–25 congenital glaucoma and, 483 Vasculogenesis, 285, 286 Thy-1 Tyrp1b, pigmentary glaucoma and, 483 Vasogenesis, blocking of, by inhaled oxygen, fl uorescent reporters under control of, 598 563 as retinal ganglion cell marker, 193 U Vax1, optic nerve development and, 201 Thy-1-GFP-H line, for study of retinal Vax1/2, chiasm patterning and, 396 ganglion cells, 599 Unmyelinated region, of optic nerve, 201, Vegf, control of retinal progenitor cell Thymidine birth dating analysis, in retina, 202f proliferation by, 328, 329 302 Usher’s syndrome, type 1b, 584 Velocity storage integrator, 94–96, 95f

Thyroid hormone receptor-β2 (TRβ2), opsins Uveitis, 513–523 Ventrolateral geniculate nucleus (vLGN), and, 305 endotoxin-induced, 513–515, 514f retinal projections to, 40, 41 Tilt, static, mouse response to, 92f, 92–93 experimental autoimmune uveitis, Vergence movements, 87, 88 Tilt vestibulo-ocular refl ex (titlVOR), 92 pathogenesis of, critical checkpoints Vestibular compensation, 99 Tilted mice, 101 in, plate 40 Vestibulo-ocular refl ex (VOR) TIMP3, gene therapy for Sorsby’s fundus experimental autoimmune uveoretinitis, angular, 88–91, 89f, 90f dystrophy using, 610 515–517 gain and response axis of, adaptation Tissue inhibitor of matrix metalloproteinase- associated with anti-tumor response to of, 96–98, 97t 1, herpes simplex virus infection and, melanoma antigen, 517 linear, 88 506 histology of, plate 39 tile (orienting), 92 Toll-like receptors (TLRs) in human lymphocyte antigen translational, 92 autoimmunity triggered by, 519–520 transgenic mice, 516 visual, 89f, 89–90 infections and, 508 induced by active immunization with Vibrissae sensitivity, measurement, 24 Tonometry, 480 retinal antigen, 515, 516t, 517f Vimentin, cataracts and, 498 Tono-Pen tonometer, 480 induced by adoptive transfer of antigen- Viral retinitis, 509 Toxoplasma gondii infections, 509 specifi c T cells, 515 Virtual optokinetic refl ex system, 112–113, Trabecular meshwork (TM), 131f, 131–132, induced by injection of antigen-pulsed 114f 132f dendritic cells, 516 Virtual optokinetic system, 20 in pigment dispersion syndrome, 484 in mice expressing a transgenic target Vision in primary open-angle glaucoma, 484 antigen in the retina, 515–516 lack of, environmental enrichment and, Transcallosal cells, binocularity and, 50–51 spontaneous, 516–517 453–455, 454f Transcription factors. See also specifi c factors immunotherapeutic approaches for, in tasks evaluating higher order cognitive cell death and, 338 522–523 functions, 25 in cornea and lens development, 699f, infectious. See Infectious eye diseases Visual ability 699–703, plate 36, plate 66 mechanisms involved in, 517–522 measures of homeobox, 699–701 antigen presentation to lymphocytes of brightness/visual detection, 16, 17f, 18 non-homeobox, 702–703 and, 519 gross, 16 photoreceptor development and, 304–305 defi cient peripheral tolerance as, of pattern discrimination, 17f, 18, 19f retinal ganglion cell development and, 194 518–519 of visual acuity, 18, 20, 21f Transforming growth factor β (TGF-β) effector cell migration, infi ltration, and in mice, 15t, 16–20 cell death and, 336 infl ammatory cell recruitment as, Visual acuity retinal vascularization and, 290–291 521 of mouse compared to other mammalian

Transforming growth factor β1 (TGF- β1), innate immune signals and, 519–520 species, 35 retinal vascularization and, 288 natural resolution mechanisms as, operational deﬁ nition of, 108 Transgene insertion, 593–594, 594f 521–522 of small vertebrate eyes, 73

index 753 Visual behavior, correlates of ocular experience-dependent, 465–473 Visual system dominance plasticity and, 447 adult ocular dominance plasticity and, development of Visual circuits, development of, retinal waves 472–473, 474f acceleration by environmental and, 348, 349f mechanisms of ocular dominance shift enrichment, plate 28 Visual cortex, 245–252 in mice and, 468–471 consolidation of visual cortical binocular monocular deprivation in juvenile mice connections and, plate 29 mapping ocular dominance in, and, 468, 469f, 470f environmental enrichment and, plate 26 stimulus-selective response potentiation 451–459, 452f, 454f, 455f, 457f, 459f, retinotopic mapping of, plate 25 and, 471–472, 472f plate 29, plate 30 callosal connections of, 46–47, 47f visually evoked potential recording special features in mouse affecting connections of, 248–251 technique and, 466, 467f, 468 research, 66–67 areal hierarchy of, 251, 251f Visual cycle, 721–729 Visual thalamus. See Lateral geniculate consolidation of, environmental cone, 727, 728f, plate 69 nucleus (LGN) enrichment and, plate 29 inhibition of formation of retinal pigment Visual vestibulo-ocular refl ex (VVOR), 89f, between different cortical areas, 249, epithelial lipofuscin fl uorophores and, 89–90 250f, 251 543f, 543–544 Visual water box, 16, 17f, 18, 20 with dorsal thalamus, 46 proteomic analysis of, 727–729 Visual water task, for measuring visual subcortical inputs and, 248 of interacting components, 727–729 perception, 110–111, 111f, 112f within V1, 248–249 retinoid, 637 Visual-somatosensory interaction, 24 with ventral thalamus and rod, genetic analysis of, 721–727, 722f, Vitamin A. See also Retinoic acid (RA) mesencephalon, 46 plate 68 defi ciency of, 364 Vi, topographic maps of, plate 8 all-trans-retinol dehydrogenase and, excess of, 364 corticotectal cells of, physiology of, 47–48 722–723 role in vision, 363 cytoarchitectonic fi elds of, 245, 246f ATP-binding cassette A4 and, 723 uptake from RBP, 725 extrastriate, in mouse compared with cellular retinaldehyde-binding protein Vogt-Koyanagi-Harada disease, 516 other mammalian species, 51–52, 52f and, 726 von Frey fi lament test, 24 extrastriate lateromedial area intracortical cellular retinol-binding protein type 1 Vpac2r, circadian photoentrainment and, connections in, plate 9, plate 10 and, 725 214 interareal feedforward and feedback 11-cis-retinol dehydrogenase and, 725 connections in, laminar organization interphotoreceptor retinoid-binding W of, plate 11 protein and, 726 intrinsic associational corticocortical isomerohydrolase and, 723–724 Water T-maze, modifi ed, 16, 17f connections of, 46 lecithin:retinol acyltransferase and, Whole-cell voltage-clamp recordings, for long-range associational corticocortical 723 retinal wave measurement, 343 connections of, 46 retinal G protein-coupled receptor and, Williams syndrome, visual cortical functions maps of, plate 7 724–725 in, 245 of mouse compared to other mammalian retinoid fl ow in visual cycle and, Wnt signaling, eye fi eld transcription factor species, 45–52 726–727 regulation by, 300–301 anatomy and, 45f, 45–47 retinol-binding protein and RBP Wolbachia, 508 binocularity and, 49–51, 50f receptor and, 725 physiology and, 47–59, 48t Visual detection, measurement of, 16, 17f, X spatial acuity and temporal resolution 18 X-linked juvenile retinoschisis (XLRS), gene and, 51–52 Visual evoked potentials (VEPs) replacement therapy for, 611 nonoriented cells of, physiology of, 47 for ocular dominance plasticity X-linked recessive familial exudative orientation selectivity of, 48–49 assessment, 439–440, plate 31 vitreoretinopathy (XLEVR), 528 relationship between cytoarchitectonic pattern electroretinographic measurement areas and topographic maps of, 248 of, 120–121, 121f Y topographically defi ned areas of, 246f, recording of, for assessing visual cortical 246–248, 247f plasticity, 466, 467f, 468 Yamamoto, Yuhiro, 270 visuotopic organization of, 45–46 Visual fi eld, of mouse compared to other Yerkes apparatus, 16, 17f Visual cortical plasticity mammalian species, 39t, 39–40, 40f, environmental enrichment and, 449–459 41f Z early-life stimulation effects on neuronal Visual function, measuring gains and losses and behavioral development and, of, behavioral methods for, 116, Zernike coeffi cients, 80 450–451 116f Zic2 neural consequences of environmental Visual pathways, organization of, plate 1 retinal ganglion cell axon divergence at enrichment and, 450 Visual phenotypes, screening of, behavioral chiasm and, 394f, 395 visual system development and, methods for, 115–116 as retinal ganglion cell marker, 193 451–459, 452f, 454f, 455f, 457f, Visual stimulation, ON and OFF pathway Zonular apparatus, 129, 130f 459f segregation and, 357–358 ZRDCT strain, 269

754 index