DOCSLIB.ORG

Dark Adaptation in Locally Detached Retina

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dark Adaptation in Locally Detached Retina Investigative Ophthalmology & Visual Science, Vol. 31, No. 7, July 1990 Copyright © Association for Research in Vision and Ophthalmology Dark Adaptation in Locally Detached Retina Toshiro Mori,* David R. Pepperberg,t and Michael F. Marmor* Nonrhegmatogenous retinal detachments were formed in the eyes of Dutch rabbits by subretinal injection of Hanks' balanced salt solution. The electroretinogram (ERG) was recorded locally from the acutely detached retina, and simultaneously from the surrounding attached retina (vitreal ERG [YERG]), before and after exposure to diffuse intense irradiation. Light adaptation elevated b-wave threshold for both the local ERG (LERG) and VERG by about 3 log units; thresholds for both responses recovered fully within 60-90 min after the irradiation. The normal time course of dark adaptation of the LERG suggests the occurrence of substantial rhodopsin regeneration in the rod photoreceptors of nonrhegmatogenously detached retina. These results differ from reports that visual pigment regeneration is slow in central serous chorioretinopathy, possibly because our detachments were studied within hours of formation, whereas some photoreceptor degeneration may be present in older clinical detachments. Invest Ophthalmol Vis Sci 31:1259-1263,1990 Under most conditions in vivo, the regeneration of ical experience that rhegmatogenous detachments rhodopsin in bleached rod photoreceptors requires typically cause an immediate loss of visual function, the delivery, to the rods, of 1 \-cis retinoid formed in measured psychophysically or electrophysiologically. the retinal pigment epithelium (RPE).1"6 Support for Even small serous detachments, such as found in pa- this view comes from studies of the isolated retina tients with central serous chorioretinopathy (CSC), preparation, in which the photoreceptors are re- are characterized by abnormally slow regeneration of moved from this RPE source of 1 l-cis retinoid. For visual pigment.13"15 However, in patients with CSC, example, after exposure to intense light, isolated ret- the focal electroretinogram (ERG) frequently re- inas ordinarily regenerate little if any rhodopsin and mains subnormal after resolution of the detachment, do not exhibit the component of electrophysiologic ie, after reassociation of the retina with the RPE.1617 recovery ("photochemical" dark adaptation7) that Thus, the retinal dysfunction in CSC may reflect de- depends on rhodopsin regeneration.89 However, the generative changes in the retina or RPE rather than, external application of l\-cis retinoid to bleached, or in addition to, the interruption of retinoid de- isolated retinas induces both the formation of rho- livery. dopsin and a substantial recovery of rod sensi- We recently have developed procedures that allow tivity.10"12 recording of the ERG from locally detached retina These findings raise a question relevant to the con- within the living rabbit eye as well as comparison of dition of retinal detachment in the living eye: To this response with the ERG generated by surrounding what extent does separation of the retina and RPE areas of attached retina.18 We report the use of this impair the delivery of 1 l-cis retinoid to the rods and technique to investigate the recovery of ERG sensitiv- thus retard or abolish photochemical dark adaptation ity in locally detached retina after strong light adapta- in the detached region of retina? We know from clin- tion.19 Since our detachments were made immedi- ately before the electrophysiologic experiments, we were able to study the effects of detachment in the From the *Department of Ophthalmology, Stanford University absence of the deteriorative changes that can develop School of Medicine, Stanford, California, and the tDepartment of Ophthalmology, University of Illinois, College of Medicine, Chi- in the retina or RPE after detachment. cago, Illinois. TM is currently affiliated with the Department of Ophthalmol- Materials and Methods ogy, Iwate Medical University, Morioka, Japan. Supported by National Institutes of Health-National Eye Insti- Experiments were performed on Dutch rabbits and tute research grants EY-01678 and EY-05831 (MFM) and adhered to the ARVO Resolution on the Use of Ani- EY-05494 and EY-01792 (DRP). DRP is a Robert E. McCormick mals in Research. We studied seven animals, which Scholar of Research to Prevent Blindness, Inc. were anesthetized with ketamine (30 mg/kg IV) and Submitted for publication: May 10, 1989; accepted November 3, urethan (1.4 g/kg IP); additional doses of ketamine 1989. Reprint requests: Michael F. Marmor, MD, Department of Oph- were given as needed. The eyes were dilated with 10% thalmology, Stanford University School of Medicine, Stanford, CA phenylephrine and 1% atropine. Local retinal de- 94305. tachments, 4-5 mm in diameter, were made as de- 1259 Downloaded from iovs.arvojournals.org on 09/29/2021 1260 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / July 1990 Vol. 31 20 scribed previously. Briefly, a glass micropipette of I£R6 tip diameter 40-50 nm was advanced through a scleral incision near the limbus until it entered the subretinal space. Hanks' balanced salt solution was injected through the micropipette to form small, functionally nonrhegmatogenous detachments. Procedures used for recording the local ERG (LERG) were similar to those described.18 In brief, a double-barrelled micropipette filled with 3 M sodium chloride agar was advanced through the scleral inci- sion so that the longer tip penetrated the detached retina through the small hole formed in creation of the detachment (Figure 1). The longer tip was posi- Fig. 2. Representative LERG and VERG responses from a dark- tioned within the subretinal space, while the shorter adapted eye to the unattenuated stimulus. Note the opposite polari- one remained in the vitreous. Signals from the mi- ties of the LERG and VERG responses. cropipettes were led through a silver-silver chloride bridge, alternating current (AC)-amplified and dis- played on a storage oscilloscope. The LERG was re- adapted eye. The LERG waveform is inverted, but corded between the tips of the subretinal and vitreal shows typical a- and b-waves. We have shown pre- electrodes. The mass, or vitreal, ERG (VERG) was viously that the LERG response arises only from de- recorded between the vitreal electrode and a reference tached retina and is free of contamination from sur- electrode on the sclera. The formation of retinal de- rounding, attached retina.18 The small size of the tachments and positioning of the recording electrodes LERG may in part reflect shunting of the transretinal were performed under dim red light. The animals current through the hole made in the formation of the were dark-adapted for an additional 30 min before detachment. Figure 3 shows the results of bleaching recording was begun. on the VERG. Before exposure to the bleaching light, ERG responses were recorded on the presentation a stimulus of —4.0 log units in intensity elicited a of 200-ms test flashes of white light from a 100-W criterion (40 nV) response. The 7-min bleach ele- lamp. The stimulating beam was controlled by an vated threshold for this criterion by 3 log units, as electronic shutter and attenuated with neutral density shown by the responses recorded § min after extinc- filters. The focused beam was led through a fiberoptic tion of the bleaching light. Over the next 90 min, guide that terminated 1 cm above the eye. The inten- threshold for the 40-/iV response returned to its origi- sity of the unattenuated light (log 1 = 0) was 8 X 103 nal level. lux at the cornea. The adapting irradiations, 7 min in Figure 4 shows LERG data recorded simulta- duration, used white light from a different source that neously with the VERG signals of Figure 3. Although produced an intensity of 6 X 105 lux at the cornea. the responses are of smaller amplitude than those of the VERG, a stimulus of log I = -4.0 was sufficient Results to elicit a detectable (20 ftV) response. Bleaching ele- Figure 2 shows representative LERG and VERG vated threshold for this criterion LERG response by responses recorded simultaneously from the dark- an extent similar to that observed for VERG thresh- old, 3 log units. At 90 min after bleaching, LERG responses were virtually identical to those recorded double-barrelled before the bleach. microelectrode Figure 5 shows the LERG and VERG thresholds from Figures 3 and 4. Figure 6 illustrates the averaged Ag-AgCI threshold data from all seven experiments of this electrode study. The thresholds for both the LERG and VERG were elevated to a similar degree (on average, about 2.6 log units) by the adapting irradiation, and thresh- olds for both responses declined with similar time retinal detachment course during the subsequent period of dark adapta- tion. In the three experiments in which thresholds Fig. 1. The recording procedure. The local ERG was recorded from the longer tip, within the retinal detachment. The ERG from were obtained at 90 min of dark adaptation, the final surrounding attached retina was recorded simultaneously from the thresholds for both the LERG and VERG were lower shorter vitreal tip. on average than those observed immediately before Downloaded from iovs.arvojournals.org on 09/29/2021 No. 7 ADAPTATION IN LOCAL DETACHMENT / Mori er ol 1261 Dark- Adapted Recovery Stimulous Intensity (Log) 90 min -4.6 Fig. 3. Example of VERG 30 min recovery after light adapta- tion. The threshold for a 40-MV criterion response was raised 3 log units by bleaching, but recovered to its original level within 90 min. 100 ^V | 50 msec light adaptation. This slight pre-bleach desensitiza- hibits complete recovery of ERG b-wave sensitivity, tion may represent a residual effect of the light with a normal time course. Since recovery of the needed for the surgical procedures. VERG and LERG exhibited similar properties, one might argue that the LERG is contaminated by elec- Discussion tric currents generated in surrounding, attached ret- The current results show that, after intense illumi- ina.
Load more

Recommended publications
  • Shedding New Light on the Generation of the Visual Chromophore PERSPECTIVE Krzysztof Palczewskia,B,C,1 and Philip D
    PERSPECTIVE Shedding new light on the generation of the visual chromophore PERSPECTIVE Krzysztof Palczewskia,b,c,1 and Philip D. Kiserb,d Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved July 9, 2020 (received for review May 16, 2020) The visual phototransduction cascade begins with a cis–trans photoisomerization of a retinylidene chro- mophore associated with the visual pigments of rod and cone photoreceptors. Visual opsins release their all-trans-retinal chromophore following photoactivation, which necessitates the existence of pathways that produce 11-cis-retinal for continued formation of visual pigments and sustained vision. Proteins in the retinal pigment epithelium (RPE), a cell layer adjacent to the photoreceptor outer segments, form the well- established “dark” regeneration pathway known as the classical visual cycle. This pathway is sufficient to maintain continuous rod function and support cone photoreceptors as well although its throughput has to be augmented by additional mechanism(s) to maintain pigment levels in the face of high rates of photon capture. Recent studies indicate that the classical visual cycle works together with light-dependent pro- cesses in both the RPE and neural retina to ensure adequate 11-cis-retinal production under natural illu- minances that can span ten orders of magnitude. Further elucidation of the interplay between these complementary systems is fundamental to understanding how cone-mediated vision is sustained in vivo. Here, we describe recent
    [Show full text]
  • Control of Rhodopsin Activity in Vision
    Control of rhodopsin DENIS A. BAYLOR, MARIE E. BURNS activity in vision Abstract high concentration in the cytoplasm in darkness and that binds to cationic channels in the Although rhodopsin's role in activating the surface membrane, holding them open. phototransduction cascade is well known, the Hydrolysis of cGMP allows the channels to processes that deactivate rhodopsin, and thus close, interrupting an inward current of sodium, the rest of the cascade, are less well calcium and magnesium ions and producing a understood. At least three proteins appear to hyperpolarisation of the membrane. The play a role: rhodopsin kinase, arrestin and hyperpolarisation reduces the rate at which recoverin. Here we review recent physiological neurotransmitter is released from the synaptic studies of the molecular mechanisms of terminal of the rod. rhodopsin deactivation. The approach was to The purpose of this paper is to review recent monitor the light responses of individual work on the important but still poorly mouse rods in which rhodopsin was altered or understood mechanisms that terminate the arrestin was deleted by transgenic techniques. light-evoked catalytic activity of rhodopsin. Removal of rhodopsin's carboxy-terminal These mechanisms, which fix the intensity and residues which contain phosphorylation sites duration of the activation of the transduction implicated in deactivation, prolonged the flash cascade, need to satisfy strong functional response 20-fold and caused it to become constraints. Rhodopsin activity must be highly variable. In rods that did not express arrestin the flash response recovered partially, terminated rapidly so that an absorbed photon but final recovery was slowed over lOO-fold.
    [Show full text]
  • Molecular Basis of Dark Adaptation in Rod Photoreceptors
    1 Molecular basis of dark c.s. LEIBROCK , T. REUTER, T.D. LAMB adaptation in rod photoreceptors Abstract visual threshold (logarithmically) against time, following 'bleaching' exposures of different Following exposure of the eye to an intense strengths. After an almost total bleach light that 'bleaches' a significant fraction of (uppermost trace) the visual threshold recovers the rhodopsin, one's visual threshold is along the classical bi-phasic curve: the initial initially greatly elevated, and takes tens of rapid recovery is due to cones, and the second minutes to recover to normal. The elevation of slower component occurs when the rod visual threshold arises from events occurring threshold drops below the cone threshold. within the rod photoreceptors, and the (Note that in this old work, the term 'photon' underlying molecular basis of these events was used for the unit now defined as the and of the rod's recovery is now becoming troland; x trolands is the illuminance at the clearer. Results obtained by exposing isolated retina when a light of 1 cd/m2 enters a pupil toad rods to hydroxylamine solution indicate with cross-sectional area x mm2.) that, following small bleaches, the primary intermediate causing elevation of visual threshold is metarhodopsin II, in its Questions and observations phosphorylated and arrestin-bound form. This The basic question in dark adaptation, which product activates transduction with an efficacy has not been answered convincingly in the six about 100 times greater than that of opsin. decades since the results of Fig. 1 were obtained, Key words Bleaching, Dark adaptation, is: Why is one not able to see very well during Metarhodopsin, Noise, Photoreceptors, the period following a bleaching exposure? Or, Sensitivity more explicitly: What is the molecular basis for the slow recovery of visual performance during dark adaptation? In considering the answers to these questions, there are three long-standing observations that need to be borne in mind.
    [Show full text]
  • Temporal and Spatial Dependence of Adaptation on Ganglion Cells
    Temporal and Spatial Dependence of Adaptation on Ganglion Cells Amin, A.P.1, Moazzezi, R.2, Werblin, F.S.2 1University of California, Berkeley; Department of Integrative Biology 2University of California, Berkeley; Department of Molecular and Cellular Biology Keywords: adaptation, contrast sensitivity, ganglion, inter-stimuli interval, ISI, lateral interneurons, luminosity, MicroElectrode Array (MEA), photoreceptor, rabbit, retina, spatial, temporal ABSTRACT BSJ One of the visual system’s many tasks is to be able to the interval between two circular stimuli (inter-stimuli distinguish objects from the background. The ability interval; ISI) of the same diameter, and by changing the to do this is limited and affected by the relationship diameter over a common ISI, we measured a ganglion between the object (or stimulus) of interest and the cell’s output for one stimulus relative to another background. Adaptation in retinal neurons is the process stimulus. The results show saturation (loss of output to of changing the cell’s response to a stimulus according the 2nd stimulus) of stimuli at lower ISIs. Also, the degree to that stimulus’s background. When the stimulus is of saturation for a given ISI depends on the diameter hard to discern from the background, the retina adapts of the stimulus. These combinations of results illustrate by improving its sensitivity to low contrast. The large the temporal and spatial dependence of adaptation response range maintained by adaptation comes at a on ganglion cells. A larger-diameter stimulus involves cost, however. Adaptation complicates neural coding by multiple neurons surrounding the ganglion cell being making the brain interpret identical stimuli as different recorded so various pathways most likely influence based on differences in background.
    [Show full text]
  • The Eye and Night Vision
    Source: http://www.aoa.org/x5352.xml Print This Page The Eye and Night Vision (This article has been adapted from the excellent USAF Special Report, AL-SR-1992-0002, "Night Vision Manual for the Flight Surgeon", written by Robert E. Miller II, Col, USAF, (RET) and Thomas J. Tredici, Col, USAF, (RET)) THE EYE The basic structure of the eye is shown in Figure 1. The anterior portion of the eye is essentially a lens system, made up of the cornea and crystalline lens, whose primary purpose is to focus light onto the retina. The retina contains receptor cells, rods and cones, which, when stimulated by light, send signals to the brain. These signals are subsequently interpreted as vision. Most of the receptors are rods, which are found predominately in the periphery of the retina, whereas the cones are located mostly in the center and near periphery of the retina. Although there are approximately 17 rods for every cone, the cones, concentrated centrally, allow resolution of fine detail and color discrimination. The rods cannot distinguish colors and have poor resolution, but they have a much higher sensitivity to light than the cones. DAY VERSUS NIGHT VISION According to a widely held theory of vision, the rods are responsible for vision under very dim levels of illumination (scotopic vision) and the cones function at higher illumination levels (photopic vision). Photopic vision provides the capability for seeing color and resolving fine detail (20/20 of better), but it functions only in good illumination. Scotopic vision is of poorer quality; it is limited by reduced resolution ( 20/200 or less) and provides the ability to discriminate only between shades of black and white.
    [Show full text]
  • Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods
    The Journal of Neuroscience, June 29, 2016 • 36(26):6973–6987 • 6973 Cellular/Molecular Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods X Justin Berry,1 XRikard Frederiksen,1 Yun Yao,2 Soile Nymark,3 Jeannie Chen,2 and Carter Cornwall1 1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, 2Zilkha Neurogenetic Institute, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, and 3Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology, 33520 Tampere, Finland Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivatedthroughreceptorphosphorylationandarrestinbinding.Fullrecoveryofreceptorsensitivityisthenachievedwhenrhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to4hindarkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphos- phorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics.
    [Show full text]
  • A Local Model of Eye Adaptation for High Dynamic Range Images
    A Local Model of Eye Adaptation for High Dynamic Range Images Patrick Ledda Luis Paulo Santos Alan Chalmers University of Bristol, UK University of Minho, Portugal University of Bristol, UK [email protected] [email protected] [email protected] ABSTRACT In the real world, the human eye is confronted with a wide range of luminances from bright sunshine to low night light. Our eyes cope with this vast range of intensities by adapta- tion; changing their sensitivity to be responsive at different illumination levels. This adaptation is highly localized, al- lowing us to see both dark and bright regions of a high dy- namic range environment. In this paper we present a new model of eye adaptation based on physiological data. The model, which can be easily integrated into existing render- ers, can function either as a static local tone mapping oper- ator for single high dynamic range image, or as a temporal adaptation model taking into account time elapsed and in- tensity of preadaptation for a dynamic sequence. We finally validate our technique with a high dynamic range display and a psychophysical study. Figure 1: On the left, the Kalabsha temple tone- mapped with our local model. On the right, linear mappings at different exposure times. Categories and Subject Descriptors I.3.3 [Computer Graphics]: Picture/Image Generation| Display Algorithms response range. Our visual system copes with the large lu- Keywords minance range by a process called adaptation. At the retina Human Visual System, Eye Adaptation, High Dynamic Range, level, eye adaptation is highly localized allowing us to see Tone Mapping both dark and bright regions in the same high dynamic range environment.
    [Show full text]
  • Dual Involvement of G-Substrate in Motor Learning Revealed by Gene Deletion
    Dual involvement of G-substrate in motor learning revealed by gene deletion Shogo Endoa,1, Fumihiro Shutohb,1, Tung Le Dinhc,1, Takehito Okamotob, Toshio Ikedad, Michiyuki Suzukie, Shigenori Kawaharae, Dai Yanagiharaf, Yamato Satof, Kazuyuki Yamadag, Toshiro Sakamotoa, Yutaka Kirinoe, Nicholas A. Hartellh, Kazuhiko Yamaguchic, Shigeyoshi Itoharad, Angus C. Nairni, Paul Greengardj, Soichi Nagaob, and Masao Itoc,2 aUnit for Molecular Neurobiology of Learning and Memory, Okinawa Institute of Science and Technology, Uruma 904-2234, Japan; bLaboratory for Motor Learning Control, cLaboratory for Memory and Learning, dLaboratory for Behavioral Genetics, and gSupport Unit for Animal Experiment, Research Resources Center, RIKEN Brain Science Institute, Wako 351-0198, Japan; eLaboratory for Neurobiophysics, School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; fDepartment of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan; hDepartment of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom; iDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06519; and jLaboratory for Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021-6399 Contributed by Masao Ito, December 30, 2008 (sent for review December 7, 2008) In this study, we generated mice lacking the gene for G-substrate, pathway acts as a modulator whose requirement for LTD may a specific substrate for cGMP-dependent protein kinase
    [Show full text]
  • Neural and Photochemical Mechanisms of Visual Adaptation in the Rat
    Neural and Photochemical Mechanisms of Visual Adaptation in the Rat JOHN E. DOWLING From the BiologicalLaboratories, Harvard University, Cambridge, Massachusetts ABSTRACT The effects of light adaptation on the increment threshold, rhodopsin content, and dark adaptation have been studied in the rat eye over a wide range of intensities. The electroretinogram threshold was used as a measure of eye sensitivity. With adapting intensities greater than 1.5 log units above the absolute ERG threshold, the increment threshold rises linearly with increasing adapting intensity. With 5 minutes of light adaptation, the rhodopsin content of the eye is not measurably reduced until the adapting in- tensity is greater than 5 log units above the ERG threshold. Dark adaptation is rapid (i.e., completed in 5 to I0 minutes) until the eye is adapted to lights strong enough to bleach a measurable fraction of the rhodopsin. After brighter light adaptations, dark adaptation consists of two parts, an initial rapid phase followed by a slow component. The extent of slow adaptation depends on the fraction of rhodopsin bleached. If all the rhodopsin in the eye is bleached, the slow fall of threshold extends over 5 log units and takes 2 to 3 hours to com- plete. The fall of ERG threshold during the slow phase of adaptation occurs in parallel with the regeneration of rhodopsin. The slow component of dark adaptation is related to the bleaching and resynthesis of rhodopsin; the fast component of adaptation is considered to be neural adaptation. INTRODUCTION It is a matter of common experience that the eye loses sensitivity in the light and regains sensitivity in the dark.
    [Show full text]
  • Early Scotopic Dark Adaptation
    Early Scotopic Dark Adaptation A dissertation presented by Rebecca J. Grayhem To The Department of Psychology In partial fulfillment of the requirements for the degree of Doctor of Philosophy In the field of Psychology Northeastern University Boston, Massachusetts December, 2010 1 EARLY SCOTOPIC DARK ADAPTATION by Rebecca J. Grayhem ABSTRACT OF DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychology in the Graduate School of Arts and Sciences of Northeastern University, December 2010 2 Abstract The human visual system can function over a broad range of light levels, from few photons to bright sunshine. I am interested in sensitivity regulation of the rod pathway in dim light, below the level at which the cones become effective. I obtained thresholds for large (1.3 deg) and tiny (5 min arc) circular test spots, either after 20-30 mins exposure to complete darkness (absolute threshold), or on uniform backgrounds of varying light intensities, or just after the background was removed to plunge the eye into darkness; Maxwellian view optics were used so that variations in pupil size would have no effect. The overall theory is that sensitivity in the rod system is adjusted by a slow process of adaptation in the retina driven by the long-term mean background light level and a rapid process sensitive to variability in the light provided by the background (“photon noise”). My data show that thresholds for tiny test spots primarily reveal the photon-driven noise effect, and those for large test spots reveal both processes. The traditional idea that all components of rod dark adaptation are slow is challenged here, since almost immediately after the background light is removed, thresholds of tiny spots drop to absolute threshold directly, and thresholds of large test spots drop half-way to absolute threshold before continuing to recover back to absolute threshold over the next 25 minutes.
    [Show full text]
  • Interruption of Homologous Desensitization in Cyclic Guanosine 3V,5V-Monophosphate Signaling Restores Colon Cancer Cytostasis by Bacterial Enterotoxins
    Research Article Interruption of Homologous Desensitization in Cyclic Guanosine 3V,5V-Monophosphate Signaling Restores Colon Cancer Cytostasis by Bacterial Enterotoxins Giovanni M. Pitari, Ronnie I. Baksh, David M. Harris, Peng Li, Shiva Kazerounian, and Scott A. Waldman Division of Clinical Pharmacology, Departments of Pharmacology and Experimental Therapeutics and Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania Abstract Bacterial heat-stable enterotoxins induce secretory diarrhea in Bacterial diarrheagenic heat-stable enterotoxins induce colon endemic populations, travelers, and animal herds (8) by serving cancer cell cytostasis by targeting guanylyl cyclase C (GCC) as superagonists for the intestine-specific receptor guanylyl signaling. Anticancer actions of these toxins are mediated by cyclase C (GCC; ref. 9). Heat-stable enterotoxins, which have cyclic guanosine 3V,5V-monophosphate (cGMP)–dependent in- evolved to facilitate bacterial dissemination and propagation, flux of Ca2+ through cyclic nucleotide-gated channels. However, exemplify molecular mimicry of the endogenous hormones prolonged stimulation of GCC produces resistance in tumor guanylin and uroguanylin, which mediate autocrine/paracrine cells to heat-stable enterotoxin–induced cytostasis. Resistance control of intestinal fluid and electrolyte homeostasis by acti- V V reflects rapid (tachyphylaxis) and slow (bradyphylaxis) mech- vating GCC and inducing cyclic guanosine 3 ,5 -monophosphate anisms of desensitization induced by cGMP. Tachyphylaxis is (cGMP)–dependent chloride efflux through the cystic fibrosis regulator channel (10–12). Intriguingly, longitudinal exposure to mediated by cGMP-dependent protein kinase, which limits the conductance of cyclic nucleotide-gated channels, reducing the heat-stable enterotoxin–producing bacteria seems to protect influx of Ca2+ propagating the antiproliferative signal from endemic populations against colon cancer by reducing rates of the membrane to the nucleus.
    [Show full text]
  • Night Vision in a Case of Vitamin a Deficiency Due to Malabsorption
    Br J Ophthalmol: first published as 10.1136/bjo.67.1.37 on 1 January 1983. Downloaded from British Journal ofOphthalmology, 1983, 67, 37-42 Night vision in a case of vitamin A deficiency due to malabsorption IDO PERLMAN,' DAVID BARZILAI,2 TAMARHAIM,3 AND ALFRED SCHRAMEK4 From the 'Department of Physiology and Biophysics, Faculty of Medicine, Technion, Haifa; the 2Department of Internal Medicine, Rambam Medical Center, Haifa; the 3Department of Ophthalmology, Rambam Medical Center, Haifa, and the 4Department of Surgery, Rambam Medical Center, Haifa, Israel SUMMARY Night vision was tested electroretinographically and psychophysically in a vitamin A deficient patient before and after therapy. Vitamin A deficiency resulted from malabsorption due to a jeujunoileal bypass operation. Before therapy the patient had severely reduced cone and rod function. After the reversal operation, accompanied by 5 injections of a total of 500000 units of vitamin A, complete recovery of cone and rod functions was observed within 7 months. Shortly after therapy rod sensitivity reached the normal level, while the time course of rod adaptation remained slower than normal and the dark-adapted electroretinographic (ERG) responses were subnormal. At later stages the ERG responses reached normal amplitudes but rod adaptation stayed slow. Only after 7 months did night vision reach the normal level with regard to the time course of rod adaptation, rod sensitivity, and ERG responses. Disturbances in night vision have long been associated in retinal function due to vitamin A deficiency and its with vitamin A deficiency. Numerous cases of night recovery following vitamin A therapy was also http://bjo.bmj.com/ blindness have been reported to arise from mal- demonstrated experimentally in rats.
    [Show full text]