Rod and cone photoreceptors possess ribbon synapses that assist in the transmission of graded light responses to second-order bipolar and horizontal cells of the vertebrate retina. Proper functioning of the synapse requires the juxtaposition of presynaptic release sites immediately adjacent to postsynaptic receptors. In this review, we focus on the synaptic, cytoskeletal, and extracellular matrix proteins that help to organize photoreceptor ribbon synapses in the outer plexiform layer. We examine the proteins that foster the clustering of release proteins, calcium channels, and synaptic vesicles in the presynaptic terminals of photoreceptors adjacent to their postsynaptic contacts. Although many proteins interact with one another in the presynaptic terminal and synaptic cleft, these protein–protein interactions do not create a static and immutable structure. Instead, photoreceptor ribbon synapses are remarkably dynamic, exhibiting structural changes on both rapid and slow time scales.

The spatial and temporal pattern of cone packing during marmoset foveal development was explored to understand the variables involved in creating a high acuity area. Retinal ages were between fetal day (Fd) 125 and 6 years. Cone density was determined in wholemounts using a new hexagonal quantification method. Wholemounts were labeled immunocytochemically with rod markers to identify reliably the foveal center. Cones were counted in small windows and density was expressed as cones × 103/mm2 (K). Two weeks before birth (Fd 125–130), cone density had a flat distribution of 20–30 K across the central retina encompassing the fovea. Density began to rise at postnatal day 1 (Pd 1) around, but not in, the foveal center and reached a parafoveal peak of 45–55 K by Pd 10. Between Pd 10 and 33, there was an inversion such that cone density at the foveal center rose rapidly, reaching 283 K by 3 months and 600 K by 5.4 months. Peak foveal density then diminished to 440 K at 6 months and older. Counts done in sections showed the same pattern of low foveal density up to Pd 1, a rapid rise from Pd 30 to 90, followed by a small decrease into adulthood. Increasing foveal cone density was accompanied by 1) a reduction in the amount of Müller cell cytoplasm surrounding each cone, 2) increased stacking of foveal cone nuclei into a mound 6–10 deep, and 3) a progressive narrowing of the rod-free zone surrounding the fovea. Retaining foveal cones in a monolayer precludes final foveal cone densities above 60 K. However, high foveal adult cone density (300 K) can be achieved by having cone nuclei stack into columns and without reducing their nuclear diameter. Marmosets reach adult peak cone density by 3–6 months postnatal, while macaques and humans take much longer. Early weaning and an arboreal environment may require rapid postnatal maturation of the marmoset fovea.

The visual pigment, rhodopsin, consists of opsin protein with 11-cis retinal chromophore, covalently bound. Light activates rhodopsin by isomerizing the chromophore to the all-trans conformation. The activated rhodopsin sets in motion a biochemical cascade that evokes an electrical response by the photoreceptor. All-trans retinal is eventually released from the opsin and reduced to vitamin A. Rod and cone photoreceptors contain vast amounts of rhodopsin, so after exposure to bright light, the concentration of vitamin A can reach relatively high levels within their outer segments. Since a retinal analog, β-ionone, is capable of activating some types of visual pigments, we tested whether vitamin A might produce a similar effect. In single-cell recordings from isolated dark-adapted salamander green-sensitive rods, exogenously applied vitamin A decreased circulating current and flash sensitivity and accelerated flash response kinetics. These changes resembled those produced by exposure of rods to steady light. Microspectrophotometric measurements showed that vitamin A accumulated in the outer segments and binding of vitamin A to rhodopsin was confirmed in in vitro assays. In addition, vitamin A improved the sensitivity of photoreceptors to ultraviolet (UV) light. Apparently, the energy of a UV photon absorbed by vitamin A transferred by a radiationless process to the 11-cis retinal chromophore of rhodopsin, which subsequently isomerized. Therefore, our results suggest that vitamin A binds to rhodopsin at an allosteric binding site distinct from the chromophore binding pocket for 11-cis retinal to activate the rhodopsin, and that it serves as a sensitizing chromophore for UV light.

Knowing neuronal types is essential for understanding the structural and functional organization of the nervous system. It has long been recognized that neuronal types should be discovered and not defined. This can be done using cluster analysis (CA). Despite there being many studies using CA to classify neurons, only a few of them meet its formal prerequisites. In the present study, we provide an example of using CA in combination with other multivariate techniques for examining neuronal diversity. A special emphasis is put on formal prerequisites to the data and procedure. The data under scrutiny are a sample of ganglion cells projecting to the basal optic nucleus [accessory optic system-projecting ganglion cells (AOS GCs)] in the common frog. There is physiological evidence that these cells comprise at least two functional types but their structural heterogeneity has not been addressed. Cells were labeled with horseradish peroxidase in vivo and examined in whole-mounted retinae using light microscopy. A sample of well-stained cells was obtained and used to estimate 18 structural parameters. A variety of clustering algorithms were used to classify the cells. The joint polar distribution of dendrite mass was monomodal. CA did not reveal a statistically reliable cluster structure in the sample. The clusters were not cohesive and well isolated. ANOVA-on-Ranks revealed no significant between-cluster differences. Our formal conclusion is that functionally distinct frog AOS GCs do not differ in morphology or dendritic arbor orientation. The advantages and limitations of the adopted approach are discussed.

We investigated the contribution of the projections from area MT to the receptive field properties of cells in visual area V2 in anesthetized and paralyzed Cebus apella monkeys. We recorded extracellular single-unit activity using tungsten microelectrodes in three monkeys before and after pressure injection of a 0.25-mol/l GABA solution. The visual stimulus consisted of a single bar moving in one of eight directions. In total, 72 V2 neurons were studied in 18 sessions of GABA injection into area MT. A group of 22 neurons was investigated over a shorter period of time ranging from 15 to 60 min, during which the activity did not return to baseline levels. The remaining 50 neurons were studied over a period of at least 2 h, and no statistical difference was observed in the neuronal response before and long after GABA inactivation. The effects on these 50 neurons consisted of an early (1–20 min) significant general decrease in excitability with changes in either orientation or direction selectivity. The differential decrease in excitability resulted in an intermediate improvement (20–40 min) of the signal-to-noise ratio for the stimulus-driven activity. The inactivation depended on the quantity of GABA injected into area MT and persisted for a period of 2 h. The GABA inactivation in area MT produced inhibition of most cells (72%) and a significant change of direction tuning in the majority (56%) of V2 neurons. Both increases and also decreases in the direction tuning of V2 neurons were observed. These feedback projections are capable of modulating not only the levels of spontaneous and driven activity of V2 neurons but also the V2 receptive field properties, such as direction selectivity.

Age-related macular degeneration (AMD) is characterized by a central vision loss. We explored the relationship between the retinal lesions in AMD patients and the processing of spatial frequencies in natural scene categorization. Since the lesion on the retina is central, we expected preservation of low spatial frequency (LSF) processing and the impairment of high spatial frequency (HSF) processing. We conducted two experiments that differed in the set of scene stimuli used and their exposure duration. Twelve AMD patients and 12 healthy age-matched participants in Experiment 1 and 10 different AMD patients and 10 healthy age-matched participants in Experiment 2 performed categorization tasks of natural scenes (Indoors vs. Outdoors) filtered in LSF and HSF. Experiment 1 revealed that AMD patients made more no-responses to categorize HSF than LSF scenes, irrespective of the scene category. In addition, AMD patients had longer reaction times to categorize HSF than LSF scenes only for indoors. Healthy participants’ performance was not differentially affected by spatial frequency content of the scenes. In Experiment 2, AMD patients demonstrated the same pattern of errors as in Experiment 1. Furthermore, AMD patients had longer reaction times to categorize HSF than LSF scenes, irrespective of the scene category. Again, spatial frequency processing was equivalent for healthy participants. The present findings point to a specific deficit in the processing of HSF information contained in photographs of natural scenes in AMD patients. The processing of LSF information is relatively preserved. Moreover, the fact that the deficit is more important when categorizing HSF indoors, may lead to new perspectives for rehabilitation procedures in AMD.

The retinal-pigmented epithelium (RPE) is critical for visual function. Throughout life, central RPE cells are lost but replenished by peripheral cell production. Glatiramer acetate increases neuronal production in mature brains and is thought to erode age-related deposits in the human retina that are risk factors for macular degeneration. Here, we ask whether this agent also elevates RPE production in mature rat eyes. If so, it may be used to replenish these cells in damaged eyes. Glatiramer acetate was given systemically for 14 days combined with Bromodeoxyuridine (BrdU) to mark cell division. One eye was then processed for the cell cycle marker Ki67 and the other for BrdU. Glatiramer acetate significantly elevated the number of RPE cells in the cell cycle, with more labeled with Ki67. There were also significantly more BrdU-labeled cells over the 14 days, confirming that some cells divided. However, while Ki67 positive cell numbers increased by approximately 100% following examination at one time point, BrdU cell numbers increased by only 3% when averaged per day. Hence, glatiramer acetate induces cells to proliferate, but many may fail either to complete division or to survive. This may have long-term consequences for this tissue.