Distal Retina Research Articles

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis.

The retina, a window into the brain, allows for the investigation of many disease-associated inflammatory and neurodegenerative changes affecting the central nervous system (CNS). Multiple sclerosis (MS), an autoimmune disease targeting the CNS, typically impacts on the visual system including the retina. Hence, we aimed to establish innovative functional retinal measures of MS-related damage, e.g., spatially resolved non-invasive retinal electrophysiology, backed by established morphological retinal imaging markers, i.e., optical coherence tomography (OCT). 20 healthy controls (HC) and 37 people with MS [17 without history of optic neuritis (NON) and 20 with (HON) history of optic neuritis] were included. In this work, we differentially assessed photoreceptor/bipolar cells (distal retina) and retinal ganglion cell (RGC, proximal retina) function besides structural assessment (OCT). We compared two multifocal electroretinography-based approaches, i.e., the multifocal pattern electroretinogram (mfPERG) and the multifocal electroretinogram to record photopic negative response (mfERG PhNR ). Structural assessment utilized peripapillary retinal nerve fiber layer thickness (pRNFL) and macular scans to calculate outer nuclear thickness (ONL) and macular ganglion cell inner plexiform layer thickness (GCIPL). One eye was randomly selected per subject. In NON, photoreceptor/bipolar cell layer had dysfunctional responses evidenced by reduced mfERG PhNR -N1 peak time of the summed response, but preserved structural integrity. Further, both NON and HON demonstrated abnormal RGC responses as evidenced by the photopic negative response of mfERG PhNR (mfPhNR) and mfPERG indices (P < 0.05). Structurally, only HON had thinned retina at the level of RGCs in the macula (GCIPL, P < 0.01) and the peripapillary area (pRNFL, P < 0.01). All three modalities showed good performance to differentiate MS-related damage from HC, 71-81% area under curve. In conclusion, while structural damage was evident mainly for HON, functional measures were the only retinal read-outs of MS-related retinal damage that were independent of optic neuritis, observed for NON. These results indicate retinal MS-related inflammatory processes in the retina prior to optic neuritis. They highlight the importance of retinal electrophysiology in MS diagnostics and its potential as a sensitive biomarker for follow-up in innovative interventions.

Extracellular K+ reflects light-evoked changes in retinal energy metabolism

Retinal neurons spend most of their energy to support the transmembrane movement of ions. Light-induced electrical activity is associated with a redistribution of ions, which affects the energy demand and results in a change in metabolism. Light-induced metabolic changes are expected to be different in distal and proximal retina due to differences in the light responses of different retinal cells. Extracellular K+ concentration ([K+]o) is a reliable indicator of local electrophysiological activity, and the purpose of this work was to compare [K+]o changes evoked by steady and flickering light in distal and proximal retina. Data were obtained from isolated mouse (C57Bl/6J) retinae. Double-barreled K+-selective microelectrodes were used to simultaneously record [K+]o and local ERGs. In the distal retina, photoreceptor hyperpolarization led to suppression of ion transfer, a decrease in [K+]o by 0.3–0.5 mM, reduced energy demand, and, as previously shown in vivo, decreased metabolism. Flickering light had the same effect on [K+]o in the distal retina as steady light of equivalent illumination. The conductance and voltage changes in postreceptor neurons are cell-specific, but the overall effect of steady light in the proximal retina is excitation, which is reflected in a [K+]o increase there (by a maximum of 0.2 mM). In steady light the [K+]o increase lasts only 1–2 s, but a sustained [K+]o increase is evoked by flickering light. A squarewave low frequency (1 Hz) flicker of photopic intensity produced the largest increases in [K+]o. Judging by measurements of [K+]o, steady illumination decreases energy metabolism in the distal retina, but not in the proximal retina (except for the first few seconds). Flickering light evokes the same decrease in the distal retina, but also evokes a sustained [K+]o increase in the proximal retina, suggesting an increase of metabolic demand there, especially at 1 Hz, when neurons of both on- and off-pathways appear to contribute maximally. This proximal retinal metabolic response to flicker correlates to the increase in blood flow during flicker that constitutes neurovascular coupling.

Penner/lgl2 is required for the integrity of the photoreceptor layer in the zebrafish retina.

ABSTRACTThe vertebrate retina is a complex tissue built from multiple neuronal cell types, which develop from a pseudostratified neuroepithelium. These cells are arranged into a highly organized and stereotypic pattern formed by nuclear and plexiform layers. The process of lamination as well as the maturation and differentiation of photoreceptor cells rely on the establishment and maintenance of apico-basal cell polarity and formation of adhesive junctions. Defects in any of these processes can result in impaired vision and are causally related to a variety of human diseases leading to blindness. While the importance of apical polarity regulators in retinal stratification and disease is well established, little is known about the function of basal regulators in retinal development. Here, we analyzed the role of Lgl2, a basolateral polarity factor, in the zebrafish retina. Lgl2 is upregulated in photoreceptor cells and in the retinal pigment epithelium by 72 h post fertilization. In both cell types, Lgl2 is localized basolaterally. Loss of zygotic Lgl2 does not interfere with retinal lamination or photoreceptor cell polarity or maturation. However, knockdown of both maternal and zygotic Lgl2 leads to impaired cell adhesion. As a consequence, severe layering defects occur in the distal retina, manifested by a breakdown of the outer plexiform layer and the outer limiting membrane. These results define zebrafish Lgl2 as an important regulator of retinal lamination, which, given the high degree of evolutionary conservation, may be preserved in other vertebrates, including human.

Molecular and functional identification of a novel photopigment in Pecten ciliary photoreceptors.

The two basic animal photoreceptor types, ciliary and microvillar, use different light-transduction schemes: their photopigments couple to Gt versus Gq proteins, respectively, to either mobilize cyclic nucleotides or trigger a lipid signaling cascade. A third class of photoreceptors has been described in the dual retina of some marine invertebrates; these present a ciliary morphology but operate via radically divergent mechanisms, prompting the suggestion that they comprise a novel lineage of light sensors. In one of these organisms, an uncommon putative opsin was uncovered that was proposed to signal through Go Orthologues subsequently emerged in diverse phyla, including mollusks, echinoderms, and chordates, but the cells in which they express have not been identified, and no studies corroborated their function as visual pigments or their suggested signaling mode. Conversely, in only one invertebrate species, Pecten irradians, have the ciliary photoreceptors been physiologically characterized, but their photopigment has not been identified molecularly. We used the transcriptome of Pecten retina to guide the cloning by polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE) extensions of a new member of this group of putative opsins. In situ hybridization shows selective transcription in the distal retina, and specific antibodies identify a single band of the expected molecular mass in Western blots and distinctly label ciliary photoreceptors in retina sections. RNA interference knockdown resulted in a reduction in the early receptor current-the first manifestation of light transduction-and prevented the prolonged aftercurrent, which requires a large buildup of activated rhodopsin. We also obtained a full-length clone of the α-subunit of a Go from Pecten retina complementary DNA and localized it by in situ hybridization to the distal photoreceptors. Small interfering RNA targeting this Go caused a specific depression of the photocurrent. These results establish this novel putative opsin as a bona fide visual pigment that couples to Go to convey the light signal.

TRPV4 Does Not Regulate the Distal Retinal Light Response.

The transient receptor potential vanilloid isoform 4 (TRPV4) functions as polymodal transducer of swelling, heat, stretch, and lipid metabolites, is widely expressed across sensory tissues, and has been implicated in pressure sensing in vertebrate retinas. Although TRPV4 knockout mice exhibit a variety of mechanosensory, nociceptive, and thermo- and osmoregulatory phenotypes, it is not known whether the transmission of light-induced signals in the eye is affected by the loss of TRPV4. We utilized field potentials, a measure of rod and cone signaling, to determine whether TRPV4 impacts on the generation and/or transmission of the photoreceptor light response and neurotransmission. Luminance intensity-response relationships were acquired in anesthetized wild-type and TRPV4-/- mice and evaluated for peak amplitude and implicit time under scotopic and photopic conditions. We found that the morphology of the outer retina is unaffected by the ablation of the Trpv4 gene. Calcium imaging of dissociated Müller glia showed that selective TRPV4 stimulation induces oscillatory calcium signals in adjacent rods. However, no differences in scotopic or photopic light-evoked signaling in the distal retina were observed in TRPV4-/- eyes, suggesting that TRPV4 signaling in healthy Müller cells does not modulate the transmission of light-evoked signals at rod and cone synapses.

The role of nitric oxide in spectral information processing in the distal turtle retina

Chromaticity type horizontal cells (C-type HCs) are the first retinal neurons exhibiting spectral information processing in cold-blooded vertebrates. The simple input of hyperpolarizing responses of cone photoreceptors is transformed in the C-type HCs into spectral opponent output. Nitric oxide (NO), a known background neuromodulator in the distal retina, was tested here for its effects upon spectral information processing by C-type HCs in the retina of turtle. Photoresponses were intracellularly recorded from C-type HCs, using light stimuli of different wavelength, applied over backgrounds of different wavelengths, and changing retinal NO level. Raising retinal level of NO in darkness by adding the precursor for its synthesis (l-Arginine) augmented the depolarizing photoresponses elicited by long-wavelength light stimuli, and reduced the hyperpolarizing photoresponses elicited by short-wavelength light stimuli. Lowering retinal level of NO by l-NAME, an inhibitor of NO synthesis, induced the opposite effects. However, the total voltage range of operation remained constant regardless of the level of NO. Qualitatively similar effects were observed under background illuminations regardless of background strength and wavelength. Altering retinal level of NO exerted a small effect upon the null wavelength. Our findings are consistent with the known effects of NO upon turtle distal retinal neurons, with the addition of NO strengthening the negative feedback pathway from L-type horizontal cells onto medium-wavelength cones.

Expression of G Proteins in the Eyes and Parietovisceral Ganglion of the Bay Scallop Argopecten irradians.

A multitude of image-forming eyes are spread across the bodies of certain invertebrates. Recent efforts have characterized how these eyes function, but less progress has been made toward describing the neural structures associated with them. Scallops, for example, have a distributed visual system that includes dozens of eyes whose optic nerves project to the lateral lobes of the parietovisceral ganglion (PVG). To identify sensory receptors and chemical synapses associated with the scallop visual system, we studied the expression of four G protein α subunits (Gαi, Gαo, Gαq, and Gαs) in the eyes and PVG of the bay scallop Argopecten irradians (Lamarck, 1819). In the eyes of A. irradians, we noted expression of Gαo by the ciliary photoreceptors of the distal retina, expression of Gαq by the rhabdomeric photoreceptors of the proximal retina, and the expression of Gαo and Gαq by the cells of the cornea; we did not, however, detect expression of Gαi or Gαs in the eyes. In the PVG of A. irradians, we noted widespread expression of Gαi, Gαo, and Gαq. The expression of Gαs was limited to fine neurites in the lateral and ventral central lobes, as well as large unipolar neurons in the dorsal central lobes. Our findings suggest that light detection by the eyes of A. irradians is conferred primarily by photoreceptors that express Gαo or Gαq, that the corneal cells of scallops may contain sensory receptors and/or receive neural input, and that G protein labeling is useful for visualizing substructures and identifying specific populations of cells within the nervous systems of invertebrates.

A Novel Method for Mouse Retinal Temperature Determination Based on ERG Photoresponses

This study introduces a novel retinal temperature determination method based on the temperature dependent properties of photoresponses recorded by electroretinography (ERG). The kinetics and amplitudes of ERG photoresponses depend on retinal temperature. Additionally, raising retinal temperature increases the probability of long-wavelength photon absorption, which manifests as temperature dependence of photoreceptor sensitivity. In this study we extract a number of features that represent these properties from the a- and b-waves of mouse ex vivo ERG flash responses and construct three multivariable regression models between temperature and the selected features. The performance of these models was evaluated against a separate test dataset and for two of the models, an RMS temperature determination error of less than 0.50 °C could be reached. Our results demonstrate that the method can be successfully used for reliable retinal temperature determination ex vivo. The method, reflecting the temperature of distal retina, can be applied also in the estimation of retinal pigment epithelium temperature.

Examining the Effects of Chromatic Aberration, Object Distance, and Eye Shape on Image-Formation in the Mirror-Based Eyes of the Bay Scallop Argopecten irradians.

The eyes of scallops form images using a concave spherical mirror and contain two separate retinas, one layered on top of the other. Behavioral and electrophysiological studies indicate that the images formed by these eyes have angular resolutions of about 2°. Based on previous ray-tracing models, it has been thought that the more distal of the two retinas lies near the focal point of the mirror and that the proximal retina, positioned closer to the mirror at the back of the eye, receives light that is out-of-focus. Here, we propose three mechanisms through which both retinas may receive focused light: (1) chromatic aberration produced by the lens may cause the focal points for longer and shorter wavelengths to fall near the distal and proximal retinas, respectively; (2) focused light from near and far objects may fall on the distal and proximal retinas, respectively; and (3) the eyes of scallops may be dynamic structures that change shape to determine which retina receives focused light. To test our hypotheses, we used optical coherence tomography (OCT), a method of near-infrared optical depth-ranging, to acquire virtual cross-sections of live, intact eyes from the bay scallop Argopecten irradians. Next, we used a custom-built ray-tracing model to estimate the qualities of the images that fall on an eye’s distal and proximal retinas as functions of the wavelengths of light entering the eye (400–700 nm), object distances (0.01–1 m), and the overall shape of the eye. When we assume 550 nm wavelength light and object distances greater than 0.01 m, our model predicts that the angular resolutions of the distal and proximal retinas are 2° and 7°, respectively. Our model also predicts that neither chromatic aberration nor differences in object distance lead to focused light falling on the distal and proximal retinas simultaneously. However, if scallops can manipulate the shapes of their eyes, perhaps through muscle contractions, we speculate that they may be able to influence the qualities of the images that fall on their proximal retinas and—to a lesser extent—those that fall on their distal retinas as well.

Choroidal and macular thickness changes in type 1 diabetes mellitus patients without diabetic retinopathy

ABSTRACTObjectives: To explore choroidal thickness (ChT) and retinal thickness (RT) changes in patients with type 1 diabetes mellitus (DM).Methods: Sixty patients with Type 1 DM and 60 age- and sex-matched healthy controls were included in this prospective case–control clinical study. All patients underwent a complete ophthalmological examination. ChT of each participant was measured at the fovea and horizontal nasal and temporal quadrants at 500-µm intervals to 1500 µm from the foveola using spectral-domain optical coherence tomography (SD-OCT). Age, gender, disease duration, serum glycosylated hemoglobin (HbA1c), fasting glucose level, axial length (AL) and refractive error were noted and analyzed.Results: Mean disease duration, mean HbA1c and mean fasting blood glucose in diabetic patients were 6.1±2.8 years, (8.9±0.9)% and 287.5±69.1 mg/dl, respectively. Age, gender, AL, spherical equivalent differences between the patients and subjects were insignificant (p>0.05). Subfoveal ChT, nasal quadrant ChT measurements, temporal 1500 µm and mean nasal ChT were significantly lower in diabetic patients (p<0.05 for all). Temporal 500 µm and 1000 µm ChT measurements, mean temporal ChT, average ChT, central macular thickness and average macular thickness did not differ significantly between the groups (p>0.05 for all).Conclusion: This study showed that there is choroidal thinning in young Type 1 diabetic patients with early period of disease duration without diabetic retinopathy nor any other systemic diseases. Choroidal changes in type 1 DM seem to begin at nasal and distal temporal retina. These results need to be verified by larger and longitudinal studies.

In Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications.

The retinal pigment epithelium (RPE) is essential for maintaining visual function. RPE derived from human induced pluripotent stem cells (iPSC-RPE) offer a promising cell-based transplantation therapy for slowing or rescuing RPE-induced visual function loss. For effective treatment, iPSC-RPE must recapitulate the physiology of native human RPE. A set of physiologically relevant functional assays are provided that assess the polarized functional activity and maturation state of the intact RPE monolayer. The present data show that donor-to-donor variability exceeds the tissue-to-tissue variability for a given donor and provides, for the first time, criteria necessary to identify iPSC-RPE most suitable for clinical application.

Destructive Changes in the Neuronal Structure of the FVB/N Mouse Retina.

We applied a series of selective antibodies for labeling the various cell types in the mammalian retina. These were used to identify the progressive loss of neurons in the FVB/N mouse, a model of early onset retinal degeneration produced by a mutation in the pde6b gene. The immunocytochemical studies, together with electroretinogram (ERG) recordings, enabled us to examine the time course of the degenerative changes that extended from the photoreceptors to the ganglion cells at the proximal end of the retina. Our study indicates that photoreceptors in FVB/N undergo a rapid degeneration within three postnatal weeks, and that there is a concomitant loss of retinal neurons in the inner nuclear layer. Although the loss of rods was detected at an earlier age during which time M- and S-opsin molecules were translocated to the cone nuclei; by 6 months all cones had also degenerated. Neuronal remodeling was also seen in the second-order neurons with horizontal cells sprouting processes proximally and dendritic retraction in rod-driven bipolar cells. Interestingly, the morphology of cone-driven bipolar cells were affected less by the disease process. The cellular structure of inner retinal neurons, i.e., ChAT amacrine cells, ganglion cells, and melanopsin-positive ganglion cells did not exhibit any gross changes of cell densities and appeared to be relatively unaffected by the massive photoreceptor degeneration in the distal retina. However, Muller cell processes began to express GFAP at their endfeet at p14, and it climbed progressively to the cell’s distal ends by 6 months. Our study indicates that FVB/N mouse provides a useful model with which to assess possible intervention strategies to arrest photoreceptor death in related diseases.

Development of the pallial eye in Nodipecten nodosus (Mollusca: Bivalvia): insights into early visual performance in scallops

Scallop pallial eyes have been the most studied optical system in bivalve mollusks. Despite recent advances in our understanding of the function and evolution of scallop eyes, little attention has been focused on eye development and early visual performance. Here, the anatomy and development of pallial eyes were investigated in the scallop Nodipecten nodosus (Linnaeus, 1758) by means of integrative microscopy techniques (i.e., light, electron, and confocal microscopy). After metamorphosis, juvenile scallops bear small papillae that rapidly transform into minute ocular organs on the middle mantle fold. The distal epithelium gradually becomes pigmented, except for the cornea formed at the distal center of the eye. Internally, the optic vesicle comprises undifferentiated cells in the distal region, while mirror plates are secreted at the base of the eye, next to pigmented cells. Within the undifferentiated cell mass, the proximal retina is the first to be formed, followed by the distal retina and then by the lens. In this respect, the late development of the scallop lens from retina precursor cells may represent a unique condition among animal eyes. Adult eyes are characterized by large pigment distribution in the epithelium, tall columnar cornea, and lens above a slightly curved double retina. Whereas the pallial eyes from adult scallops are a complex visual system based on a mirror mechanism to form a focused image on the retina, early eye condition suggests a simple degree of directional photoreception, with no spatial vision.

Opposite effects of ethanol on electroretinographic ON and OFF responses are due to its action in the distal retina

Abstract The aim of the present study was to give insight into the mechanisms of action of ethanol on the function of retinal ON and OFF channels. In order to fulfill this aim the effects of ethanol on the electroretinographic (ERG) ON

ON-OFF Interactions in the Retina: Role of Glycine and GABA.

In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells and it apparently remains as signals propagate to higher brain visual centers. A fundamental question in visual neuroscience is how these two parallel pathways function: are they independent from each other or do they interact somehow? In the latter case, what kinds of mechanisms are involved and what are the consequences from this cross-talk? This review summarizes current knowledge about the types of interactions between the ON and OFF channels in nonmammalian and mammalian retina. Data concerning the ON-OFF interactions in distal retina revealed by recording of single bipolar cell activity and electroretinographic ON (b-wave) and OFF (d-wave) responses are presented. Special emphasis is put on the ON-OFF interactions in proximal retina and their dependence on the state of light adaptation in mammalian retina. The involvement of the GABAergic and glycinergic systems in the ON-OFF crosstalk is also discussed.

How aquatic water-beetle larvae with small chambered eyes overcome challenges of hunting under water.

A particularly unusual visual system exists in the visually guided aquatic predator, the Sunburst Diving Beetle, Thermonectus marmoratus (Coleoptera: Dytiscidae). The question arises: how does this peculiar visual system function? A series of experiments suggests that their principal eyes (E1 and E2) are highly specialized for hunting. These eyes are tubular and have relatively long focal lengths leading to high image magnification. Their retinae are linear, and are divided into distinct green-sensitive distal and UV and polarization-sensitive proximal portions. Each distal retina, moreover, has many tiers of photoreceptors with rhabdomeres the long axis of which are peculiarly oriented perpendicular to the light path. Based on detailed optical investigations, the lenses of these eyes are bifocal and project focused images onto specific retinal tiers. Behavioral experiments suggest that these larvae approach prey within their eyes' near-fields, and that they can correctly gauge prey distances even when conventional distance-vision mechanisms are unavailable. In the near-field of these eyes object distance determines which of the many retinal layers receive the best-focused images. This retinal organization could facilitate an unusual distance-vision mechanism. We here summarize past findings and discuss how these eyes allow Thermonectus larvae to be such successful predators.

Notch signaling differentially regulates Atoh7 and Neurog2 in the distal mouse retina.

Notch signaling regulates basic helix-loop-helix (bHLH) factors as an evolutionarily conserved module, but the tissue-specific mechanisms are incompletely elucidated. In the mouse retina, bHLH genes Atoh7 and Neurog2 have distinct functions, with Atoh7 regulating retinal competence and Neurog2 required for progression of neurogenesis. These transcription factors are extensively co-expressed, suggesting similar regulation. We directly compared Atoh7 and Neurog2 regulation at the earliest stages of retinal neurogenesis in a broad spectrum of Notch pathway mutants. Notch1 and Rbpj normally block Atoh7 and Neurog2 expression. However, the combined activities of Notch1, Notch3 and Rbpj regulate Neurog2 patterning in the distal retina. Downstream of the Notch complex, we found the Hes1 repressor mediates Atoh7 suppression, but Hes1, Hes3 and Hes5 do not regulate Neurog2 expression. We also tested Notch-mediated regulation of Jag1 and Pax6 in the distal retina, to establish the appropriate context for Neurog2 patterning. We found that Notch1;Notch3 and Rbpj block co-expression of Jag1 and Neurog2, while specifically stimulating Pax6 within an adjacent domain. Our data suggest that Notch signaling controls the overall tempo of retinogenesis, by integrating cell fate specification, the wave of neurogenesis and the developmental status of cells ahead of this wave.

Role of dopamine in distal retina.

Dopamine is the most abundant catecholamine in the vertebrate retina. Despite the description of retinal dopaminergic cells three decades ago, many aspects of their function in the retina remain unclear. There is no consensus among the authors about the stimulus conditions for dopamine release (darkness, steady or flickering light) as well as about its action upon the various types of retinal cells. Many contradictory results exist concerning the dopamine effect on the gross electrical activity of the retina [reflected in electroretinogram (ERG)] and the receptors involved in its action. This review summarized current knowledge about the types of the dopaminergic neurons and receptors in the retina as well as the effects of dopamine receptor agonists and antagonists on the light responses of photoreceptors, horizontal and bipolar cells in both nonmammalian and mammalian retina. Special focus of interest concerns their effects upon the diffuse ERG as a useful tool for assessment of the overall function of the distal retina. An attempt is made to reveal some differences between the dopamine actions upon the activity of the ON versus OFF channel in the distal retina. The author has included her own results demonstrating such differences.

Glycinergic feedback enhances synaptic gain in the distal retina

Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole cell recordings, intracellular recordings and specific antibody labelling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the postsynaptic glycine currents from axon-detached bipolar cells while stimulating presynaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors and suppresses the uptake of glutamate by the type 2A excitatory amino acid transporter on photoreceptors. The net effect is a significant increase in synaptic gain between photoreceptors and their second-order neurons.

Ionotropic GABA Receptors and Distal Retinal ON and OFF Responses.

In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells in distal retina. The activity of large populations of ON and OFF bipolar cells is reflected in the b- and d-waves of the diffuse electroretinogram (ERG). The role of gamma-aminobutyric acid (GABA), acting through ionotropic GABA receptors in shaping the ON and OFF responses in distal retina, is a matter of debate. This review summarized current knowledge about the types of the GABAergic neurons and ionotropic GABA receptors in the retina as well as the effects of GABA and specific GABAA and GABAC receptor antagonists on the activity of the ON and OFF bipolar cells in both nonmammalian and mammalian retina. Special emphasis is put on the effects on b- and d-waves of the ERG as a useful tool for assessment of the overall function of distal retinal ON and OFF channels. The role of GABAergic system in establishing the ON-OFF asymmetry concerning the time course and absolute and relative sensitivity of the ERG responses under different conditions of light adaptation in amphibian retina is also discussed.