Population Of Retinal Ganglion Cells Research Articles

Functional characterization of retinal ganglion cells using tailored nonlinear modeling

The mammalian retina encodes the visual world in action potentials generated by 20–50 functionally and anatomically-distinct types of retinal ganglion cell (RGC). Individual RGC types receive synaptic input from distinct presynaptic circuits; therefore, their responsiveness to specific features in the visual scene arises from the information encoded in synaptic input and shaped by postsynaptic signal integration and spike generation. Unfortunately, there is a dearth of tools for characterizing the computations reflected in RGC spike output. Therefore, we developed a statistical model, the separable Nonlinear Input Model, to characterize the excitatory and suppressive components of RGC receptive fields. We recorded RGC responses to a correlated noise (“cloud”) stimulus in an in vitro preparation of mouse retina and found that our model accurately predicted RGC responses at high spatiotemporal resolution. It identified multiple receptive fields reflecting the main excitatory and suppressive components of the response of each neuron. Significantly, our model accurately identified ON-OFF cells and distinguished their distinct ON and OFF receptive fields, and it demonstrated a diversity of suppressive receptive fields in the RGC population. In total, our method offers a rich description of RGC computation and sets a foundation for relating it to retinal circuitry.

Topical bromfenac transiently delays axotomy-induced retinal ganglion cell loss

Optic nerve axotomy in rodents allows detailed studies of the effect of different treatments on the survival of central nervous system neurons, the retinal ganglion cells (RGCs). Here we have analyzed the neuroprotective effect of topical bromfenac treatment, a nonsteroidal anti-inflammatory drug (NSAID) used in clinic to ameliorate post-operative inflammation, on axotomized rat RGCs. The left optic nerve of adult rats was subjected to optic nerve crush (ONC). Half of the rats were treated with a topical instillation of saline. On the other half, immediately after the surgery, 2 drops of bromfenac (0.09% Yellox; Bausch & Lomb) were instilled, and then every 12 h until analysis. Retinas in both groups were dissected 3, 5, 7, 9 and 14 days after ONC (n = 4–8/time point/group). Toxicity of bromfenac was assessed in intact retinas treated during 14 days (n = 6). Intact untreated retinas were used as control of the RGC population. RGCs were identified by Brn3a immunodetection and automatically quantified. Our results show that bromfenac does not cause RGC loss in intact retinas. In the injured groups, the number of RGCs at 7, 9 and 14 days after the lesion was significantly higher in treated vs. untreated retinas. To our knowledge this is the first report showing that a topical treatment with a NSAIDs delays axotomy-induced RGC loss and indicates that treatment with NSAIDs could be used as conjunctive therapy in diseases that proceed with optic nerve damage.

Mouse dLGN Receives Functional Input from a Diverse Population of Retinal Ganglion Cells with Limited Convergence

Mouse vision is based on the parallel output of more than 30 functional types of retinal ganglion cells (RGCs). Little is known about how representations of visual information change between retina and dorsolateral geniculate nucleus (dLGN) of the thalamus, the main relay between retina and cortex. Here, we functionally characterized responses of retrogradely labeled dLGN-projecting RGCs and dLGN neurons to the same set of visual stimuli. We found that many of the previously identified functional RGC types innervate dLGN, which maintained a high degree of functional diversity. Using a linear model to assess functional connectivity between RGC types and dLGN neurons, we found that responses of dLGN neurons could be predicted as linear combination of inputs from on average five RGC types, but only two of those had the strongest functional impact. Thus, mouse dLGN receives functional input from a diverse population of RGC types with limited convergence.

Stimulation strategies for selective activation of retinal ganglion cell soma and threshold reduction

Objective. Retinal prosthetic implants restore partial vision to patients blinded due to outer retinal degeneration, using a camera-guided multielectrode array (MEA) that electrically stimulates surviving retinal neurons. Commercial epi-retinal prostheses use millisecond-scale charge-balanced, symmetric, cathodic-first biphasic pulses to depolarize retinal ganglion cells (RGCs) and bipolar cells (BCs), frequently creating oblong perceptions of light related to axonal activation of RGCs. Stimulation strategies that avoid axonal stimulation and decrease the threshold of targeted neurons may significantly improve prosthetic vision in terms of spatial resolution and power efficiency. Approach. We developed a virus-transduced genetically encoded calcium indicator (GECI) GCaMP6f and microscopy platform for calcium imaging to record the neural activity from RGCs at single-cell resolution in wholemount retinas. Multiple stimulation paradigms were applied through a microelectrode array (MEA) with transparent indium tin oxide electrodes. The evoked neuronal activities were converted to corresponding 2D calcium imaging transient pattern and spatial threshold map to identify the ideal focal response which corresponds to optimal percept in patient. Main results. The proposed optical system with GCaMP6f is capable of recording from population of mouse RGCs in real time during electrical stimulation with precise location information relative to the stimulation sites. Optimal duration and phase order of pulse were identified to avoid axonal stimulation and selectively activate targeted RGC somas, without requiring a significant increase in stimulation charge. Additionally, we show that reduced stimulus threshold can be achieved with the special design of asymmetric anodic-first pulse. Significance. Our findings support the possibility of manipulating the responses of RGCs through varying the stimulation waveform. Focal response can be achieved with relative short duration (⩽120 μs) pulses, and can be improved by reversing the standard phase order. The RGCs threshold can be significantly reduced by 33.3%–50% in terms of charge through applying hyperpolarizing pre-pulses with a 20:1 ratio (pre-pulse:stimulus pulse). The results support the future retinal prosthesis design that potentially forms more ideal shape perception with higher spatial resolution and power efficiency.

Speed-Selectivity in Retinal Ganglion Cells is Sharpened by Broad Spatial Frequency, Naturalistic Stimuli

Motion detection represents one of the critical tasks of the visual system and has motivated a large body of research. However, it remains unclear precisely why the response of retinal ganglion cells (RGCs) to simple artificial stimuli does not predict their response to complex, naturalistic stimuli. To explore this topic, we use Motion Clouds (MC), which are synthetic textures that preserve properties of natural images and are merely parameterized, in particular by modulating the spatiotemporal spectrum complexity of the stimulus by adjusting the frequency bandwidths. By stimulating the retina of the diurnal rodent, Octodon degus with MC we show that the RGCs respond to increasingly complex stimuli by narrowing their adjustment curves in response to movement. At the level of the population, complex stimuli produce a sparser code while preserving movement information; therefore, the stimuli are encoded more efficiently. Interestingly, these properties were observed throughout different populations of RGCs. Thus, our results reveal that the response at the level of RGCs is modulated by the naturalness of the stimulus - in particular for motion - which suggests that the tuning to the statistics of natural images already emerges at the level of the retina.

Advances in the Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells.

Human pluripotent stem cell (hPSC) technology has revolutionized the field of biology through the unprecedented ability to study the differentiation of human cells in vitro. In the past decade, hPSCs have been applied to study development, model disease, develop drugs, and devise cell replacement therapies for numerous biological systems. Of particular interest is the application of this technology to study and treat optic neuropathies such as glaucoma. Retinal ganglion cells (RGCs) are the primary cell type affected in these diseases, and once lost, they are unable to regenerate in adulthood. This necessitates the development of strategies to study the mechanisms of degeneration as well as develop translational therapeutic approaches to treat early- and late-stage disease progression. Numerous protocols have been established to derive RGCs from hPSCs, with the ability to generate large populations of human RGCs for translational applications. In this review, the key applications of hPSCs within the retinal field are described, including the use of these cells as developmental models, disease models, drug development, and finally, cell replacement therapies. In greater detail, the current report focuses on the differentiation of hPSC-derived RGCs and the many unique characteristics associated with these cells in vitro including their genetic identifiers, their electrophysiological activity, and their morphological maturation. Also described is the current progress in the use of patient-specific hPSCs to study optic neuropathies affecting RGCs, with emphasis on the use of these RGCs for studying disease mechanisms and pathogenesis, drug screening, and cell replacement therapies in future studies.

Functional Diversity in the Retina Improves the Population Code.

Within a given brain region, individual neurons exhibit a wide variety of different feature selectivities. Here, we investigated the impact of this extensive functional diversity on the population neural code. Our approach was to build optimal decoders to discriminate among stimuli using the spiking output of a real, measured neural population and compare its performance against a matched, homogeneous neural population with the same number of cells and spikes. Analyzing large populations of retinal ganglion cells, we found that the real, heterogeneous population can yield a discrimination error lower than the homogeneous population by several orders of magnitude and consequently can encode much more visual information. This effect increases with population size and with graded degrees of heterogeneity. We complemented these results with an analysis of coding based on the Chernoff distance, as well as derivations of inequalities on coding in certain limits, from which we can conclude that the beneficial effect of heterogeneity occurs over a broad set of conditions. Together, our results indicate that the presence of functional diversity in neural populations can enhance their coding fidelity appreciably. A noteworthy outcome of our study is that this effect can be extremely strong and should be taken into account when investigating design principles for neural circuits.

A 3D Convolutional Neural Network to Model Retinal Ganglion Cell's Responses to Light Patterns in Mice.

Deep Learning offers flexible powerful tools that have advanced our understanding of the neural coding of neurosensory systems. In this work, a 3D Convolutional Neural Network (3D CNN) is used to mimic the behavior of a population of mice retinal ganglion cells in response to different light patterns. For this purpose, we projected homogeneous RGB flashes and checkerboards stimuli with variable luminances and wavelength spectrum to mimic a more naturalistic stimuli environment onto the mouse retina. We also used white moving bars in order to localize the spatial position of the recorded cells. Then recorded spikes were smoothed with a Gaussian kernel and used as the output target when training a 3D CNN in a supervised way. To find a suitable model, two hyperparameter search stages were performed. In the first stage, a trial and error process allowed us to obtain a system that is able to fit the neurons firing rates. In the second stage, a systematic procedure was used to compare several gradient-based optimizers, loss functions and the model's convolutional layers number. We found that a three layered 3D CNN was able to predict the ganglion cells firing rates with high correlations and low prediction error, as measured with Mean Squared Error and Dynamic Time Warping in test sets. These models were either competitive or outperformed other models used already in neuroscience, as Feed Forward Neural Networks and Linear-Nonlinear models. This methodology allowed us to capture the temporal dynamic response patterns in a robust way, even for neurons with high trial-to-trial variable spontaneous firing rates, when providing the peristimulus time histogram as an output to our model.

Photoreceptive retinal ganglion cells control the information rate of the optic nerve

Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information reaching the eye and ask whether a neural measure of irradiance can therefore be used to proactively control information flow along the optic nerve. We first show that firing rates for the retina's output neurons [retinal ganglion cells (RGCs)] scale with irradiance and are positively correlated with rates of information and the gain of visual responses. Irradiance modulates firing in the absence of any other visual signal confirming that this is a genuine response to changing ambient light. Irradiance-driven changes in firing are observed across the population of RGCs (including in both ON and OFF units) but are disrupted in mice lacking melanopsin [the photopigment of irradiance-coding intrinsically photosensitive RGCs (ipRGCs)] and can be induced under steady light exposure by chemogenetic activation of ipRGCs. Artificially elevating firing by chemogenetic excitation of ipRGCs is sufficient to increase information flow by increasing the gain of visual responses, indicating that enhanced firing is a cause of increased information transfer at higher irradiance. Our results establish a retinal circuitry driving changes in RGC firing as an active response to alterations in ambient light to adjust the amount of visual information transmitted to the brain.

Separating intrinsic interactions from extrinsic correlations in a network of sensory neurons

Correlations in sensory neural networks have both extrinsic and intrinsic origins. Extrinsic or stimulus correlations arise from shared inputs to the network, and thus depend strongly on the stimulus ensemble. Intrinsic or noise correlations reflect biophysical mechanisms of interactions between neurons, which are expected to be robust to changes of the stimulus ensemble. Despite the importance of this distinction for understanding how sensory networks encode information collectively, no method exists to reliably separate intrinsic interactions from extrinsic correlations in neural activity data, limiting our ability to build predictive models of the network response. In this paper we introduce a general strategy to infer {population models of interacting neurons that collectively encode stimulus information}. The key to disentangling intrinsic from extrinsic correlations is to infer the {couplings between neurons} separately from the encoding model, and to combine the two using corrections calculated in a mean-field approximation. We demonstrate the effectiveness of this approach on retinal recordings. The same coupling network is inferred from responses to radically different stimulus ensembles, showing that these couplings indeed reflect stimulus-independent interactions between neurons. The inferred model predicts accurately the collective response of retinal ganglion cell populations as a function of the stimulus.

Neural Mechanisms of Motion Processing in the Mammalian Retina.

Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.

Selective Vulnerability of αOFF Retinal Ganglion Cells during Onset of Autoimmune Optic Neuritis

Retinal ganglion cells (RGCs), a diverse body of neurons which relay visual signals from the retina to the higher processing regions of the brain, are susceptible to neurodegenerative processes in several diseases affecting the retina. Previous evidence shows that RGCs are damaged at early stages of autoimmune optic neuritis (AON), prior to subsequent degeneration of the optic nerve. In order to study cell type-specific vulnerability of RGCs we performed immunohistochemical and patch-clamp electrophysiological analyses of RGCs following induction of AON using the experimental autoimmune encephalomyelitis model in Brown Norway rats. We report that αRGCs are more susceptible to degeneration than the global RGC population as a whole, with functional and structural changes beginning even prior to demyelination and inflammatory infiltration of the optic nerve (where the RGC axons reside). Functional classification of αRGCs into OFF-sustained, OFF-transient and ON-sustained subtypes revealed that αOFF RGCs (both sustained and transient subtypes) are more vulnerable than αON RGCs, as indicated by reductions in light-evoked post-synaptic currents and retraction of dendritic arbours. Classification of neuronal susceptibility is a first step in furthering our understanding of what underlies a neuron’s vulnerability to degenerative processes, necessary for the future development of effective neuroprotective strategies.

Simulation of retinal ganglion cell response using fast independent component analysis.

Advances in neurobiology suggest that neuronal response of the primary visual cortex to natural stimuli may be attributed to sparse approximation of images, encoding stimuli to activate specific neurons although the underlying mechanisms are still unclear. The responses of retinal ganglion cells (RGCs) to natural and random checkerboard stimuli were simulated using fast independent component analysis. The neuronal response to stimuli was measured using kurtosis and Treves-Rolls sparseness, and the kurtosis, lifetime and population sparseness were analyzed. RGCs exhibited significant lifetime sparseness in response to natural stimuli and random checkerboard stimuli. About 65 and 72% of RGCs do not fire all the time in response to natural and random checkerboard stimuli, respectively. Both kurtosis of single neurons and lifetime response of single neurons values were larger in the case of natural than in random checkerboard stimuli. The population of RGCs fire much less in response to random checkerboard stimuli than natural stimuli. However, kurtosis of population sparseness and population response of the entire neurons were larger with natural than random checkerboard stimuli. RGCs fire more sparsely in response to natural stimuli. Individual neurons fire at a low rate, while the occasional "burst" of neuronal population transmits information efficiently.

Mouse dLGN Receives Input from a Diverse Population of Retinal Ganglion Cells with Limited Functional Convergence

In the mouse, the parallel output of more than 30 functional types of retinal ganglion cells (RGCs) serves as the basis for all further visual processing. Little is known about how the representation of visual information changes between the retina and the dorsolateral geniculate nucleus (dLGN) of the thalamus, the main relay station between the retina and cortex. Here, we functionally characterized responses of retrogradely labeled dLGN-projecting RGCs and dLGN neurons to the same set of visual stimuli. We found that many of the previously identified functional RGC types innervate the dLGN, which maintained a high degree of functional diversity. Using a linear model to assess functional connectivity between RGC types and dLGN neurons, we found that the responses of dLGN neurons could be predicted as a linear combination of inputs from on average five RGC types, but only two of those had the strongest functional impact. Thus, mouse dLGN receives input from a diverse population of RGCs with limited functional convergence.

Elevated Pressure Increases Ca2+ Influx Through AMPA Receptors in Select Populations of Retinal Ganglion Cells.

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca2+ (CI-AMPAR). However, some AMPA receptors are permeable to Ca2+ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs we first show that acute exposure to elevated pressure increased expression of Ca2+-permeable AMPA receptors (CP-AMPARs) in some, but not all classes of RGCs. When RGCs were sampled without regard to subtype, AMPA currents, measured using patch clamp recording, were blocked by the CP-AMPAR blocker PhTX-74 to a greater extent in pressure-treated RGCs vs. control. Furthermore, imaging experiments revealed an increase in Ca2+ influx during AMPA application in pressure-treated RGCs. However, examination of specific RGC subtypes using reporter lines revealed striking differences in both baseline AMPAR composition and modulation of this baseline composition by stress. Notably, ON alpha RGCs identified using the Opn4 mouse line and immunohistochemistry, had low expression of CP-AMPARs. Conversely, an ON-OFF direction selective RGC and putative OFF alpha RGC each expressed high levels of CP-AMPARs. These differences between RGC subtypes were also observed in RGCs from whole retina. Elevated pressure further lowered expression of CP-AMPARs in ON alpha RGCs, but raised expression in ON-OFF and OFF RGCs. Changes in CP-AMPAR expression following challenge with elevated pressure were correlated with RGC survival: ON alpha RGCs were unaffected by application of pressure, while the number of putative OFF alpha RGCs declined by approximately 50% following challenge with pressure. Differences in expression of CP-AMPARs between RGC subtypes may form the underpinnings for subtype-specific synaptic plasticity. Furthermore, the differential responses of these RGC subtypes to elevated pressure may contribute to the reported resistance of ON alpha, and susceptibility of OFF and ON-OFF RGCs to injury in models of glaucoma.

Survival of melanopsin expressing retinal ganglion cells long term after optic nerve trauma in mice

In this study we have compared the response to optic nerve crush (ONC) and to optic nerve transection (ONT) of the general population of retinal ganglion cells in charge of the image-forming visual functions that express Brn3a (Brn3a+RGCs) with that of the sub-population of non-image forming RGCs that express melanopsin (m+RGCs). Intact animals were used as control. ONT and ONC were performed at 0.5 mm from the optic disk, and retinas dissected 3, 5, 7, 14, 30, 45 or 90 days later (n = 5/injury/time point). In all the retinas, Brn3a+RGCs and m+RGCs were identified and their survival analyzed quantitatively and topographically. There were no differences in the course of RGC loss between lesions. The decrease of RGCs was significant at short time points (3 or 5 days for Brn3a+ or m+ RGCs, respectively) and, up to 14 days, the course of loss of both RGC populations was similar, surviving at this time point between 20 and 22% of their original population. However, while the loss of Brn3a+RGCs continues steadily up to 90 days when only 5–6% of them still remain, the loss of m+RGCs stops at 14 days, and the proportion of surviving m+RGCs remains constant up to 90 days (26–30%). In conclusion, m+RGC do not respond to axotomy in the same way than the rest of RGCs, and so whilst image-forming RGCs die in two exponential phases a quick one and a slow protracted one, non-image forming RGCs die only during the first quick phase.

NMDA Receptors Contribute to Retrograde Synaptic Transmission from Ganglion Cell Photoreceptors to Dopaminergic Amacrine Cells.

Recently, a line of evidence has demonstrated that the vertebrate retina possesses a novel retrograde signaling pathway. In this pathway, phototransduction is initiated by the photopigment melanopsin, which is expressed in a small population of retinal ganglion cells. These ganglion cell photoreceptors then signal to dopaminergic amacrine cells (DACs) through glutamatergic synapses, influencing visual light adaptation. We have previously demonstrated that in Mg2+-containing solution, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors mediate this glutamatergic transmission. Here, we demonstrate that removing extracellular Mg2+ enhances melanopsin-based DAC light responses at membrane potentials more negative than −40 mV. Melanopsin-based responses in Mg2+-free solution were profoundly suppressed by the selective N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5. In addition, application of NMDA to the retina produced excitatory inward currents in DACs. These data strongly suggest that DACs express functional NMDA receptors. We further found that in the presence of Mg2+, D-AP5 reduced the peak amplitude of melanopsin-based DAC responses by ~70% when the cells were held at their resting membrane potential (−50 mV), indicating that NMDA receptors are likely to contribute to retrograde signal transmission to DACs under physiological conditions. Moreover, our data show that melanopsin-based NMDA-receptor-mediated responses in DACs are suppressed by antagonists specific to either the NR2A or NR2B receptor subtype. Immunohistochemical results show that NR2A and NR2B subunits are expressed on DAC somata and processes. These results suggest that DACs express functional NMDA receptors containing both NR2A and NR2B subunits. Collectively, our data reveal that, along with AMPA receptors, NR2A- and NR2B-containing NMDA receptors mediate retrograde signal transmission from ganglion cell photoreceptors to DACs.

Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and asymmetrically distributed in the mouse retina.

A small population of retinal ganglion cells expresses the photopigment melanopsin and function as autonomous photoreceptors. They encode global luminance levels critical for light-mediated non-image forming visual processes including circadian rhythms and the pupillary light reflex. There are five melanopsin ganglion cell subtypes (M1-M5). M1 and displaced M1 (M1d) cells have dendrites that ramify within the outermost layer of the inner plexiform layer. It was recently discovered that some melanopsin ganglion cells extend dendrites into the outer retina. Outer Retinal Dendrites (ORDs) either ramify within the outer plexiform layer (OPL) or the inner nuclear layer, and while present in the mature retina, are most abundant postnatally. Anatomical evidence for synaptic transmission between cone photoreceptor terminals and ORDs suggests a novel photoreceptor to ganglion cell connection in the mammalian retina. While it is known that the number of ORDs in the retina is developmentally regulated, little is known about the morphology, the cells from which they originate, or their spatial distribution throughout the retina. We analyzed the morphology of melanopsin-immunopositive ORDs in the OPL at different developmental time points in the mouse retina and identified five types of ORDs originating from either M1 or M1d cells. However, a pattern emerges within these: ORDs from M1d cells are generally longer and more highly branched than ORDs from conventional M1 cells. Additionally, we found ORDs asymmetrically distributed to the dorsal retina. This morphological analysis provides the first step in identifying a potential role for biplexiform melanopsin ganglion cell ORDs.

Multipolar Field Shaping in a Suprachoroidal Visual Prosthesis.

Visual prostheses are now an available mobility aid for patients blinded by degenerative retinal diseases. However, the spatial resolution of existing devices is still insufficient to deliver normal levels of mobility vision without stimulation strategies, which enable existing devices to deliver several different percepts per stimulation site. A stimulation strategy, in which field shaping is achieved by incorporating multipolar (bipolar and tripolar) stimulation could convey additional information to a user of a visual prosthesis, as compared with monopolar stimulation, is investigated. Electrical stimulus response thresholds were simulated using morphologically and physiologically accurate cable models of human retinal ganglion cell (RGC) axons. From the population response patterns which could be evoked in simulation, multipolar field-shaping stimulation from one location could convey as much information as monopolar array stimulation. This result is confirmed in vitro by applying a Bayesian classification analysis to multielectrode array recordings of RGC population responses to extracellular stimulation. In vitro recorded population responses to individual stimuli in vitro could be used to train a Baysian classifier, which could correctly identify individual stimuli as predicted by the simulated population responses. In both simulation and in vitro experiments, monopolar thresholds were not significantly different to multipolar thresholds.

Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina

In this work we study the effects of an acute light-induced retinal degeneration on the population of melanopsin positive retinal ganglion cells (m+RGCs) and the expression of the melanopsin protein in the retina. The m+RGCs may be more resistant than other RGCs to lesion, but the effects of an acute light exposure in this population are unknown. Albino rats were exposed to white light (3000 lux) continuously for 48 h and processed 0, 3, 7 or 30 days after light exposure (ALE). Whole-mounted retinas were immunodetected with antibodies against melanopsin, Brn3a, and rhodopsin to study the populations of m+RGC, Brn3a+RGC and rods (which are the most abundant photoreceptors in the rat retina). Three days ALE there was substantial rod loss in an arciform area of the superior retina and with time this loss expanded in the form of rings all throughout the retina. Light exposure did not affect the number of Brn3a+RGCs but diminished the numbers of m+RGCs. Immediately ALE there was a significant decrease in the mean number of immunodetected m+RGCs that was more marked in the superior retina. Later, the number of m+RGCs increased progressively and reached normal values one month ALE. Western blot analysis showed that melanopsin expression down-regulates shortly ALE and recovers thereafter, in accordance with the anatomical data. This study demonstrates that there is a transient downregulation of melanopsin expression in the RGCs during the first month ALE. Further studies would be needed to clarify the long-term effect of light exposure on the m+RGC population.