The Influence of Different Retinal Subcircuits on the Nonlinearity Of
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Retinal Ganglion Cell Loss Is Size Dependent in Experimental Glaucoma
Investigative Ophthalmology & Visual Science, Vol. 32, No. 3, March 1991 Copyright © Association for Research in Vision and Ophthalmology Retinal Ganglion Cell Loss Is Size Dependent in Experimental Glaucoma Yoseph Glovinsky,* Harry A. Quigley,f and Gregory R. Dunkelbergerf Thirty-two areas located in the temporal midperipheral retina were evaluated in whole-mount prepara- tions from four monkeys with monocular experimental glaucoma. Diameter frequency distributions of remaining ganglion cells in the glaucomatous eye were compared with corresponding areas in the normal fellow eye. Large cells were significantly more vulnerable at each stage of cell damage as determined by linear-regression analysis. The magnitude of size-dependent loss was moderate at an early stage (20% loss), peaked at 50% total cell loss, and decreased in advanced damage (70% loss). In glaucomatous eyes, the lower retina had significantly more large cell loss than the corresponding areas of the upper retina. In optic nerve zones that matched the retinal areas studied, large axons selectively were damaged first. Psychophysical testing aimed at functions subserved by larger ganglion cells is recommended for detection and follow-up of early glaucoma; however, assessment of functions unique to small cells is more appropriate for detecting change in advanced glaucoma. Invest Ophthalmol Vis Sci 32:484-491, 1991 Current psychophysical tests do not detect glau- tage of ideal cellular preservation. Eyes with mild, comatous damage until a substantial minority of reti- moderate, and late damage were evaluated. In addi- nal ganglion cells have died.1'2 To develop more sen- tion, we correlated the damage patterns in the retinas sitive tests, a comprehensive understanding of the and optic nerves of the glaucomatous eyes. -
The Effect of Retinal Ganglion Cell Injury on Light-Induced Photoreceptor Degeneration
The Effect of Retinal Ganglion Cell Injury on Light-Induced Photoreceptor Degeneration Robert J. Casson,1 Glyn Chidlow,1 John P. M. Wood,1 Manuel Vidal-Sanz,2 and Neville N. Osborne1 PURPOSE. To determine the effect of optic nerve transection photoreceptors against light-induced injury. An unusual aspect (ONT) and excitotoxic retinal ganglion cell (RGC) injury on of the ONT-induced photoreceptor protection is that it specif- light-induced photoreceptor degeneration. ically affects the retinal ganglion cells (RGCs), yet subsequently METHODS. Age- and sex-matched rats underwent unilateral ONT protects the outer retina. This phenomenon implies the exis- D tence of retrograde communication systems within the retina, or received intravitreal injections of N-methyl- -aspartate 5,6 (NMDA). The fellow eye received sham treatment, and 7 or 21 possibly involving Mu¨ller cells and FGF-2, but does not days later each eye was subjected to an intense photic injury. exclude the possibility that the effect is specific to ONT. A Maximum a- and b-wave amplitudes of the flash electroretino- nonspecific effect would suggest that similar responses might gram (ERG) were measured at baseline, after the RGC insult, be occurring in a wide range of optic neuropathies. We hy- and 5 days after the photic injury. Semiquantitative reverse pothesized that the protective effect of ONT may be a gener- transcription-polymerase chain reaction analysis and immuno- alizable effect and that other forms of inner retinal injury such blot analysis were used to assess rod opsin mRNA and rhodop- as excitotoxic injury may also protect against LIPD. Further- sin kinase protein levels and to measure defined trophic factors more, although FGF-2 has been implicated as the agent respon- 7 or 21 days after ONT or injection of NMDA. -
Anatomy and Physiology of the Afferent Visual System
Handbook of Clinical Neurology, Vol. 102 (3rd series) Neuro-ophthalmology C. Kennard and R.J. Leigh, Editors # 2011 Elsevier B.V. All rights reserved Chapter 1 Anatomy and physiology of the afferent visual system SASHANK PRASAD 1* AND STEVEN L. GALETTA 2 1Division of Neuro-ophthalmology, Department of Neurology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA 2Neuro-ophthalmology Division, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA INTRODUCTION light without distortion (Maurice, 1970). The tear–air interface and cornea contribute more to the focusing Visual processing poses an enormous computational of light than the lens does; unlike the lens, however, the challenge for the brain, which has evolved highly focusing power of the cornea is fixed. The ciliary mus- organized and efficient neural systems to meet these cles dynamically adjust the shape of the lens in order demands. In primates, approximately 55% of the cortex to focus light optimally from varying distances upon is specialized for visual processing (compared to 3% for the retina (accommodation). The total amount of light auditory processing and 11% for somatosensory pro- reaching the retina is controlled by regulation of the cessing) (Felleman and Van Essen, 1991). Over the past pupil aperture. Ultimately, the visual image becomes several decades there has been an explosion in scientific projected upside-down and backwards on to the retina understanding of these complex pathways and net- (Fishman, 1973). works. Detailed knowledge of the anatomy of the visual The majority of the blood supply to structures of the system, in combination with skilled examination, allows eye arrives via the ophthalmic artery, which is the first precise localization of neuropathological processes. -
Imaging and Quantifying Ganglion Cells and Other Transparent Neurons in the Living Human Retina
Imaging and quantifying ganglion cells and other transparent neurons in the living human retina Zhuolin Liua,1, Kazuhiro Kurokawaa, Furu Zhanga, John J. Leeb, and Donald T. Millera aSchool of Optometry, Indiana University, Bloomington, IN 47405; and bPurdue School of Engineering and Technology, Indiana University–Purdue University Indianapolis, Indianapolis, IN 46202 Edited by David R. Williams, University of Rochester, Rochester, NY, and approved October 18, 2017 (received for review June 30, 2017) Ganglion cells (GCs) are fundamental to retinal neural circuitry, apoptotic GCs tagged with an intravenously administered fluores- processing photoreceptor signals for transmission to the brain via cent marker (14), thus providing direct monitoring of GC loss. The their axons. However, much remains unknown about their role in second incorporated adaptive optics (AO)—which corrects ocular vision and their vulnerability to disease leading to blindness. A aberrations—into SLO sensitive to multiply-scattered light (12). major bottleneck has been our inability to observe GCs and their This clever combination permitted imaging of a monolayer of GC degeneration in the living human eye. Despite two decades of layer (GCL) somas in areas with little or no overlying nerve fiber development of optical technologies to image cells in the living layer (NFL) (see figure 5, human result of Rossi et al.; ref. 12). By human retina, GCs remain elusive due to their high optical trans- contrast, our approach uses singly scattered light and produces lucency. Failure of conventional imaging—using predominately sin- images of unprecedented clarity of translucent retinal tissue. This gly scattered light—to reveal GCs has led to a focus on multiply- permits morphometry of GCL somas across the living human ret- scattered, fluorescence, two-photon, and phase imaging techniques ina. -
The Horizontal Raphe of the Human Retina and Its Watershed Zones
vision Review The Horizontal Raphe of the Human Retina and its Watershed Zones Christian Albrecht May * and Paul Rutkowski Department of Anatomy, Medical Faculty Carl Gustav Carus, TU Dresden, 74, 01307 Dresden, Germany; [email protected] * Correspondence: [email protected] Received: 24 September 2019; Accepted: 6 November 2019; Published: 8 November 2019 Abstract: The horizontal raphe (HR) as a demarcation line dividing the retina and choroid into separate vascular hemispheres is well established, but its development has never been discussed in the context of new findings of the last decades. Although factors for axon guidance are established (e.g., slit-robo pathway, ephrin-protein-receptor pathway) they do not explain HR formation. Early morphological organization, too, fails to establish a HR. The development of the HR is most likely induced by the long posterior ciliary arteries which form a horizontal line prior to retinal organization. The maintenance might then be supported by several biochemical factors. The circulation separate superior and inferior vascular hemispheres communicates across the HR only through their anastomosing capillary beds resulting in watershed zones on either side of the HR. Visual field changes along the HR could clearly be demonstrated in vascular occlusive diseases affecting the optic nerve head, the retina or the choroid. The watershed zone of the HR is ideally protective for central visual acuity in vascular occlusive diseases but can lead to distinct pathological features. Keywords: anatomy; choroid; development; human; retina; vasculature 1. Introduction The horizontal raphe (HR) was first described in the early 1800s as a horizontal demarcation line that extends from the macula to the temporal Ora dividing the temporal retinal nerve fiber layer into a superior and inferior half [1]. -
Neuromodulation of Ganglion Cell Photoreceptors
NEUROMODULATION OF GANGLION CELL PHOTORECEPTORS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Puneet Sodhi, B.S. Graduate Program in Neuroscience The Ohio State University 2015 Dissertation Committee: Dr. Andrew TE Hartwick, Advisor Dr. Karl Obrietan Dr. Stuart Mangel Dr. Heather Chandler Copyright by Puneet Sodhi 2015 ABSTRACT Intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a rare subset of ganglion cells in the mammalian retina that are primarily involved in non-image forming (NIF) visual processes. In the presence of light, ipRGC photoreceptors exhibit sustained depolarization, in contrast to the transient hyperpolarizing responses of rod and cone photoreceptors. The persistence of this response with light offset underlies the reduced temporal resolution exhibited by these ipRGCs. The overall aim of this thesis was to determine whether the unique temporal dynamics of ipRGC photoresponses are subject to modification by endogenous retinal neuromodulators. As post-synaptic photoreceptors, ipRGCs are capable of integrating photic information transmitted from pre-synaptic neurons regulated by rod- and cone-driven signaling. Given that ipRGCs possess dense dendritic nets that span the entire retina, I hypothesized that these ganglion cell photoreceptors were capable of being modulated by extrinsic input from the retinal network. Using multi-electrode array recordings on rat retinas, I demonstrated that the duration of light-evoked ipRGC spiking can be modified through an intracellular cAMP/PKA-mediated signaling pathway. Specifically, stimulation of the cAMP/PKA pathway leads to prolonged ipRGC light responses. Expanding upon these findings, I next identified an endogenous retinal neuromodulator capable of modulating ipRGC photoresponses through this signaling pathway. -
Direct Inputs to Off Α and G9 Ganglion Cells from Aii Amacrine Cells in Rabbit Retina
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2010 DIRECT INPUTS TO OFF Α AND G9 GANGLION CELLS FROM AII AMACRINE CELLS IN RABBIT RETINA Wei-Li Liu Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Cells Commons, and the Other Neuroscience and Neurobiology Commons Recommended Citation Liu, Wei-Li, "DIRECT INPUTS TO OFF Α AND G9 GANGLION CELLS FROM AII AMACRINE CELLS IN RABBIT RETINA" (2010). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 81. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/81 This Thesis (MS) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. DIRECT INPUTS TO OFF Α AND G9 GANGLION CELLS FROM AII AMACRINE CELLS IN RABBIT RETINA A THESIS Presented to the Faculty of The University of Texas Health Science Center at Houston and The University of Texas M. D. Anderson Cancer Center Graduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE by Wei-Li Liu B.S. -
Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA Is Conveyed Through Wide-Field Amacrine Cells
The Journal of Neuroscience, January 17, 2018 • 38(3):723–732 • 723 Cellular/Molecular Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA Is Conveyed through Wide-Field Amacrine Cells Amanda M. Travis,1 XStephanie J. Heflin,2 XArlene A. Hirano,3,6 Nicholas C. Brecha,3,4,5,6 and XVadim Y. Arshavsky1,2 1Department of Pharmacology and 2Department of Ophthalmology, Duke University, Durham, North Carolina 27710, 3Department of Neurobiology, 4Department of Medicine, and 5Department of Ophthalmology, Stein Eye Institute David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, and 6Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073 The vertebrate retina has the remarkable ability to support visual function under conditions of limited illumination, including the processing of signals evoked by single photons. Dim-light vision is regulated by several adaptive mechanisms. The mechanism explored in this study is responsible for increasing the light sensitivity and operational range of rod bipolar cells, the retinal neurons operating immediately downstream of rod photoreceptors. This sensitization is achieved through the sustained dopamine-dependent GABA re- lease from other retinal neurons. Our goals were to identify the cell type responsible for the GABA release and the site of its modulation by dopamine. Previous studies have suggested the involvement of amacrine and/or horizontal cells. We now demonstrate, using mice of both sexes, that horizontal cells do not participate in this mechanism. Instead, sustained GABA input is provided by a subpopulation of wide-field amacrine cells, which stimulate the GABAC receptors at rod bipolar cell axons. -
Selective Loss of Retinal Ganglion Cells in Albino Avian Glaucoma
Investigative Ophthalmology & Visual Science, Vol. 29, No. 6, June 1988 Copyright © Association for Research in Vision and Ophthalmology Selective Loss of Retinal Ganglion Cells in Albino Avian Glaucoma Koichi Takatsuji,* Masaya Tohyama,t Yoshio 5ato4 and Akira Nakamura§ Retinal ganglion cell loss was investigated in the retinae of albino quails before and after the develop- ment of glaucoma. The isodensity maps of ganglion cells, the total number of ganglion cells, and the histograms of the cell size in the central region of the retina were similar between albino quails without glaucoma and pigmented quails. However, ganglion cells in the intermediate and peripheral regions of the albino quail retina without glaucoma were significantly smaller than those of the pigmented quail retina. In albino quails with moderate glaucoma in 3 months of age, 11% to 55% of all the retinal ganglion cells had disappeared, with the loss of medium-sized cells (30-60 urn2) occurring earlier than that of small and large cells. In albino quails with advanced glaucoma, there was marked cupping around the optic nerve head, and only small ganglion cells remained in the ganglion cell layer. Invest Ophthalmol Vis Sci 29:901-909,1988 We found imperfect albino mutant quails with a coma, paying particular attention to the ganglion sex-linked recessive gene.12 These quails have white cells most affected. feathers except on their back, and ruby-colored eyes instead of brown. There are few pigment granules in Materials and Methods the pigment epithelium, choroid and pecten oculi. Albino mutant quails (Coturnix cotumix japonica, Some pigment granules, however, were noted in the gene symbol at) at 3 (n = 11) and 6 (n = 8) months of ora serrata, ciliary processes and iris.3 After the age of age, and 6-month-old pigmented quails (n = 5) were 3 months, these quails develop closed-angle glau- used. -
Introduction to the Retina
Introduction to the Retina Andrew Stockman NEUR 0017 Visual Neuroscience Optics An image of an object is focused by the cornea and lens onto the rear surface of the eye: the retina. Inverted image Accommodation: Focus on near objects by contracting Ciliary muscle and changing shape of lens. Eye and retina Retinal cells Cajal’s (1909-1911) neural architecture drawing based on the Golgi method. FOVEAL PIT Optic Tectum (superior colliculus) • Ramon y Cajal noted that neurons have anatomical polarity. • No myelination in the retina • Myelination of axons in the optic nerve Retina: a light sensitive part of the CNS OUTER LIMITING MEMBRANE OUTER NUCLEAR LAYER OUTER PLEXIFORM LAYER Light microscopic INNER NUCLEAR LAYER vertical section INNER PLEXIFORM LAYER GANGLION CELL LAYER INNER LIMITING MEMBRANE “Plexiform”: weblike or complex Retina: a light sensitive part of the CNS Schematic vertical section Light microscopic vertical section LIGHT Electrophysiological recording methods Extracellular recordings Single neurone (unit) spikes Microelectrode 500uV Flash neurone Field Potential Recording Flash Electrophysiological recording methods Whole cell (Patch Extracellular recordings clamp) recordings Single neurone (unit) spikes Microelectrode 500uV isolated whole Membrane patch cell currents Flash neurone Patch clamping can use: Field Potential Recording (1) Voltage clamp technique in which the voltage across the cell membrane is controlled by the experimenter and the resulting currents are recorded. (2) Current clamp technique in which the current -
Circuit Mechanisms of a Retinal Ganglion Cell with Stimulus-Dependent Response Latency and Activation Beyond Its Dendrites
Article Circuit Mechanisms of a Retinal Ganglion Cell with Stimulus-Dependent Response Latency and Activation Beyond Its Dendrites Highlights Authors d Unusual receptive field properties appear in a mouse retinal Adam Mani, Gregory W. Schwartz ganglion cell (RGC) Correspondence d Latency decreases with stimulus size and the RGC is [email protected] activated beyond its dendrites In Brief d Mechanisms of these phenomena involve inhibition and disinhibition Mani and Schwartz report the discovery of the ‘‘ON delayed’’ retinal ganglion cell d This RGC may be involved in signaling image focus (RGC) and describe its unusual receptive field properties. Synaptic mechanisms underlying this receptive field highlight new roles for inhibition and disinhibition in retinal circuits. The authors suggest a function for the ON delayed RGC in non- image-forming vision. Mani & Schwartz, 2017, Current Biology 27, 471–482 February 20, 2017 ª 2016 Elsevier Ltd. http://dx.doi.org/10.1016/j.cub.2016.12.033 Current Biology Article Circuit Mechanisms of a Retinal Ganglion Cell with Stimulus-Dependent Response Latency and Activation Beyond Its Dendrites Adam Mani1 and Gregory W. Schwartz1,2,3,4,* 1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 2Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 3Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA 4Lead Contact *Correspondence: [email protected] http://dx.doi.org/10.1016/j.cub.2016.12.033 SUMMARY responses, and circuit mechanisms responsible for such specific responses have only been identified for a handful of Center-surround antagonism has been used as the RGC types among the 40 types thought to exist in the mamma- canonical model to describe receptive fields of lian retina [12]. -
Morphological and Lmmunocytochemical Identification of Indoleamine-Accumulating Neurons in the Cat Retina
The Journal of Neuroscience, May 1987, 7(5): 1574-I 585 Morphological and lmmunocytochemical Identification of Indoleamine-Accumulating Neurons in the Cat Retina H. Wlssle, T. Voigt, and B. Pate1 Max-Planck-lnstitut ftir Hirnforschung, 6000 Frankfurt/M. 71, Federal Republic of Germany The type and distribution of indoleamine-accumulating neu- Indoleaminesare preferentially accumulatedby amacrine cells rons were studied in the cat retina. The neurons were char- in all mammals.The synaptic organization of theselabeled neu- acterized by their capacity to take up an exogenous indole- rons has been extensively studied, and it has been found that amine, 5,6-dihydroxytryptamine, which could then be their terminals engagein reciprocal synapseswith bipolar cell visualized using formaldehyde-induced fluorescence. Under terminals and provide synaptic contacts with other amacrine direct microscopic control, intracellular injection of Lucifer cells (Ehinger and Holmgren, 1979; Dowling et al., 1980; Holm- yellow into the labeled cells revealed that the indoleamine- gren-Taylor, 1982). accumulating neurons comprise 2 distinct morphological However, there is an absenceof detailed information con- types of amacrine cell and 1 class of ganglion cell. The cerning the morphological types and density distribution of in- dendritic morphology and retinal distribution of these cells doleamine-accumulatingneurons in the cat. The present paper were studied in detail. The proportion of retinal cells that provides a description of the dendritic branching pattern and accumulate 5-HT was measured using 5-HT (5-hydroxytrypt- retinal distribution of these neurons. Their morphology was amine) preloading in vitro and immunocytochemistry with an revealed by a technique developed for cholinergic amacrinecells anti-5-HT antibody.