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OPA1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina.

PURPOSE: Autosomal dominant optic atrophy is a hereditary disorder characterized by progressive loss of vision and caused by mutations in a dynamin-related gene, OPA1, which translates into a protein with a mitochondrial leader sequence. In this study the OPA1 gene and its protein were localized in the rat and mouse retina, and its rat orthologue, rOpa1, was identified. METHODS: The rOpa1 cDNA was isolated by using reverse transcribed cDNA from total RNA obtained from a rat retinal ganglion cell line. The spatial and temporal expression patterns of OPA1 and its gene product were investigated by RNA in situ hybridization and immunohistochemistry in mouse and rat retinas. To characterize further the OPA1-positive neurons, retinal ganglion cells were retrogradely labeled by an immunogold fluorescent tracer or double labeled with OPA1 and choline acetyltransferase or calbindin antibodies. RESULTS: Protein sequence alignment revealed a 96% identity between rat and human OPA1 mRNA. OPA1 expression was found as early as postnatal day 3 in the developing rodent retina. In the mature retina, the OPA1 gene and its protein were found not only in retinal ganglion cells, but also in starburst amacrine cells and horizontal cells, both of which are involved in lateral signal processing within the retina. However, OPA1 was absent from mitochondria rich nerve fibers and photoreceptor indicating a specific role for OPA1 in signal processing rather than in the requirement of mitochondrial energy supply in the retina. CONCLUSIONS: The data suggest an important and specific function of the OPA1 protein, not only in the optic nerve forming ganglion cells but also in the intrinsic signal processing of the inner retina.

Animals↗

Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy.

The dopaminergic pathway that affects rod-driven horizontal cells has been studied in the Royal College of Surgeons (RCS) rat during the period preceding photoreceptor degeneration (postnatal day 17-24). The experiments were performed by intracellular recording from single horizontal cells in vitro. Horizontal cells from the recessive control animals (postnatal day 17-24) were depolarized by dopamine (10 microM) and hyperpolarized by the D1 antagonist SCH 23,390 (10 microM). In contrast, cells from age-matched dystrophic retinas, though depolarized by dopamine, were unaffected by SCH 23390 (10-100 microM), suggesting a significant reduction in the level of endogenous dopamine release. Histologic examination for catecholaminergic neurons revealed no differences in either the cell number or anatomy between the retinas of the control and dystrophic animals. Furthermore, perfusion of the control retinas with melatonin (500 nM-1 microM) yielded response characteristic of the dystrophic type. In the period preceding degeneration, the RCS retina thus displays a discrete abnormality in dopaminergic pathways, such that there is a gross reduction in endogenous dopamine release below that required to activate D1 receptors. Since melatonin levels have been shown to be high in these retinas, we propose that abnormalities in the dopamine-melatonin systems give rise to an electrophysiologic deficit in the postphotoreceptoral retina of the RCS rat.

Animals↗

Two groups of TH-like immunoreactive neurons in the frog (Rana pipiens) retina.

The morphology and distribution of TH-like immunoreactive (TH-IR) cells in the retina of Rana pipiens were studied in retinal whole mounts and in radial and horizontal sections. A large majority (96%) of the immunoreactive cells were found in the inner nuclear layer while a few cells were found in the ganglion cell layer. All TH-IR cells had round to oval somata with average diameter of 10 microm. The 2-4 primary processes of these cells distributed extensively to sublamina 1 of the inner plexiform layer (IPL) and sparsely to sublamina 5. Two groups of TH-IR cells were distinguished: one, designated thin cells, had only thin (<2 microm diameter) primary processes; the second, designated thick cells, had one or more primary processes with diameter(s) exceeding 2 microm for a distance of 5 microm or more from the soma. The thin cells did not significantly differ from the thick cells in soma diameter, number of primary processes, horizontal spread of processes or vertical lamination of processes. Nearest neighbor analyses of the two types revealed that the population of TH-IR cells (thick and thin together) have an orderly distribution while the thick cells alone are more randomly distributed, indicating that the thick cells do not comprise a functional population. The total number of TH-IR cells varied between retinas; the variability was due principally to variation of thin cell density. It is hypothesized that the thick cells are a subpopulation of the TH-IR cells which are in a particular physiological state at the time of fixation.

Animals↗

[Implication of GABA in the spatial organization of the receptive fields of retinal ganglia cells of frogs].

An histoautoradiographic study of the Chicken and Frog retinae was made following an intravitreal injection if tritiated GABA. This amino acid was especially fixed at the amacrine and horizontal cell level. It has been suggested (Werblin, 1974) that horizontal cells might be responsible for the spatial organization of the receptive fields of retinal ganglion cells. GABA could thus be involved in bringing about of the centre-surround arrangement of the latter receptive fields. We have shown that picrotoxin, a specific GABA-antagonist, does indeed provoke marked changes in the activity of retinal ganglion cells. It provokes a decrease in the response threshold, a facilitation of spontaneous activities, and a marked increase in the receptive field area of the ON-OFF ganglion cells: from 12 at the start, it reaches 24 under the effect of picrotoxin.

Aminobutyrates↗

Density, soma size, and regional distribution of rabbit retinal ganglion cells.

Cell soma area or diameter distributions are generally very skewed and present some unusual problems in characterization and description. In this study of ganglion cell soma size in rabbit retina, our conclusions are based on a statistical method which not only characterizes this particular neuronal population but which also may be of considerable value in other species and other parts of the nervous system. To facilitate comparisons between retinas, we used ganglion cell density as the measure of retinal location. The rabbit retina has a horizontally extended area centralis, the visual streak, which we show to have a uniformly high peak cell density along most of its length. Cell density maps were used to estimate the total number of ganglion cells in the retina; the mean for three retinas was about 406,000 cells, which corresponds well to an earlier count of optic nerve axons (394,000 +/- 20,000; Vaney, D.I., and A. Hughes (1976) J. Comp. Neurol. 170: 241-252). Contrary to other reports, we could not find any large differences in ganglion cell size distributions between the inferior peripheral retina and the visual streak nor could we confirm the report of a large cell area temporalis (Provis, J. M. (1979) J. Comp. Neurol. 185: 121-138). Cell size distributions in the superior and inferior retina were very different, however, and, within the inferior retina, there was a small but systematic change in cell size between the periphery and the visual streak. In general, small and medium size cells were present in nearly constant proportions throughout the inferior retina, while the large ganglion cells showed a small decrease in proportion from the periphery to the visual streak; the decline in large cells was a linear function of cell density. In terms of ganglion cell soma size, there was no sharp distinction between the visual streak and the peripheral retina.

Animals↗

What do retinal müller (glial) cells do for their neuronal 'small siblings'?

Müller (radial glial) cells are the predominant glia of the vertebrate retina. They arise, together with rod photoreceptor cells, bipolar cells, and a subset of amacrine cells, from common precursor cells during a late proliferative phase. One Müller cell and a species-specific number of such neurons seem to form a columnar unit within the retinal tissue. In contrast, 'extracolumnar neurons' (ganglion cells, cone photoreceptor cells, horizontal cells, and another subset of amacrine cells) are born and start differentiation before most Müller cells are generated. It may be essential for such neurons to develop metabolic capacities sufficient to support their own survival, whereas late-born ('columnar') neurons seem to depend on a nursing function of their 'sisterly' Müller cell. Thus, out of the cell types within a retinal column it is exclusively the Müller cell that possesses the enzymes for glycogen metabolism. We present evidence that Müller cells express functional insulin receptors. Furthermore, isolated Müller cells rapidly hydrolyse glycogen when they are exposed to an elevated extracellular K+ ion concentration, a signal that is involved in the regulation of neuronal-glial metabolic cooperation in the brain. Müller cells are also thought to be essential for rapid and effective retinal K+ homeostasis. We present patch-clamp measurements on Müller cells of various vertebrate species that all demonstrate inwardly rectifying K+ channels; this type of channel is well-suited to mediate spatial buffering currents. A mathematical model is presented that allows estimation of Müller cell-mediated K+ currents. A simulation analysis shows that these currents greatly limit lateral spread of excitation beyond the borders of light-stimulated retinal columns, and thus help to maintain visual acuity.

Animals↗

Kainate activation of horizontal, bipolar, amacrine, and ganglion cells in the rabbit retina.

Patterns of excitation in populations of retinal bipolar, amacrine, and ganglion cells were mapped by activating alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) and kainate (KA) receptors with KA in the presence of the channel-permeant guanidinium analogue 1-amino-4-guanidobutane (AGB). Registered serial thin sections were probed with immunoglobulins targeting AGB, glutamate, glycine, and gamma-aminobutyric acid (GABA) to visualize KA-evoked responses and the neurochemical signatures of distinct cell types. OFF-center cone bipolar cells and both type A and type B horizontal cells were strongly activated by KA. ON-center cone bipolar cells displayed weak AGB signals that arose at least partially, if not entirely, from coupling with KA-responsive glycinergic amacrine cells, whereas rod bipolar cells exhibited no detectable AGB permeation after KA activation. GABA-positive amacrine cells displayed a range of KA responses, some possessing little AGB signal even after strong KA activation, whereas all identifiable glycine-positive amacrine cells were driven by KA. Quantitative agonist responsivities of cells in the ganglion cell layer revealed that starburst amacrine cells are the most KA-responsive cell type in that layer. Ganglion cells varied in KA responsivity across morphologic subtypes, with a large alpha-like ganglion cell group the being the most KA responsive. Some ganglion cells displayed weak KA responses, even with saturating doses, that may have been be due to an absence of AMPA/KA receptors or to the existence of AGB-impermeant AMPA/KA receptor complexes.

Agmatine↗

The distribution of displaced ganglion cells in the retina of the pigeon.

Displaced ganglion cells in the pigeon's retina, at the inner margin of the inner nuclear layer, were labelled by retrograde axonal transport of horseradish peroxidase (HRP). Large HRP injections were made in order to fill all the retinal projection sites in the thalamus and midbrain. The distribution of labelled cells was studied in retinal whole mounts incubated with tetramethyl benzidine (TMB) substrate for HRP. A maximum of 5,300 HRP labelled displaced ganglion cells was found. They were concentrated in a band of retina centred on the horizontal meridian, with high density areas (of about 110 cells/mm2) near the area centralis and in the mid-temporal retina. This is a different distribution to that of ganglion and inner nuclear layer cells; these are concentrated in the area centralis and red field. The orientation of retinal maps was checked by ophthalmoscopic measurements of the angle of the pecten to the horizontal in alert pigeons; this was found to be approximately 70 degrees. The array of displaced ganglion cells, studied by nearest neighbour distributions, was irregular and nearly random, which is consistent with a system of low spatial acuity. In the central retina only the cell bodies and not the dendrites of small displaced ganglion cells (7.5 microns diameter) were labelled; towards the periphery large displaced ganglion cells (16 microns diameter) with 2-5 radially arranged primary dendrites were found.

Animals↗

Dopamine modulation of GABAC receptor function in an isolated retinal neuron.

1. Dopamine modulation of gamma-aminobutyric acid (GABA)-elicited currents was studied in cone horizontal cells acutely isolated from the catfish retina using the whole-cell patch-clamp technique. 2. GABA puffs elicited both a GABAC current and a transporter current. Dopamine (10 microM) in the bath selectively reduced the GABAC receptor current without affecting the GABA transporter current. 3. This effect of dopamine was mimicked by the D1 agonist SKF38393 (25 microM) and an adenylyl cyclase activator forskolin (20 microM) but blocked by the dopamine antagonist haloperidol (30 microM). 4. These findings provide the first evidence for dopamine modulation of GABA receptor function in the vertebrate nervous system. In the intact retina, dopamine may modulate GABA-mediated chemical coupling and autofeedback in horizontal cells.

Animals↗

[Retinal neuronal cell death: molecular mechanism and neuroprotection].

In retinitis pigmentosa, retinal detachment, age-related macular degeneration, and glaucoma, retinal neuronal cells are damaged by a common mechanism, apoptosis. Because apoptosis is an active process that requires de novo expression of a "death message", this process can be controlled by inhibiting the expression of the "death message". We first studied whether a retinal ischemia-reperfusion model can be used as a model for retinal neuronal apoptosis. In the retinal ischemia-reperfusion injuries, typical features of apoptosis, including TUNEL-positive cells, DNA ladder formation, and ultrastructural features of apoptosis were found. Using the model, systematic research to identify the "death message" was done by DNA microarray analysis. About 200 messages were found to be up- or down-regulated during the process of retinal ischemia-reperfusion. These genes were divided into four groups: (1) transcription factor genes, (2) cell cycle-related genes, (3) reactive oxygen scavenger genes and (4) molecular chaperon genes. The possible roles of such genes in neuronal apoptosis following retinal ischemia-reperfusion injury were studied. In the model, reactive oxygen species produced by reperfusion was found to generate lipid peroxides and induced up-regulation of a transcription factor, c-Jun, that further induced aberrant expression of cell cycle-related genes such as cyclin D1 in amacrine cells. However, because no controlled expression of cell cycle-related genes takes place in retinal neurons, amacrine cells died by a G1 arrest mechanism. On the other hand, horizontal cells never expressed cyclin D1 and the cells were found to die by necrosis. The study revealed a possible mechanism of retinal neuronal apoptosis and it also became apparent that different types of neurons use different "death messages". Furthermore, the possibility that inhibition of a "death message" sometimes induces necrosis rather than apoptosis was shown. This means that we need to try inhibition of the death mechanism upstream rather than downstream. Administration of thioredoxin, an endogenous reactive oxygen species that blocks generation of lipid peroxides and thus inhibits the death process upstream, was found to be neuroprotective against retinal ischemia-reperfusion injury. Aberrant expression of c-Jun and cyclin D1 was down-regulated by the treatment. Possible roles of caspases were also studied by using the ischemia-reperfusion injury, RCS rat, and excessive light exposure damage in wild type and caspase-1 deficient mice. Also, application of adeno-associated virus that carries Bcl-xL was tested to find possible neuroprotective effects on RCS rats. Our studies showed that caspase-1 played a more important role in the retinal photoreceptors and caspase-3 was important in neurons in the inner nuclear layer. Caspase-2 was found to be a major caspase in the retinal ganglion cell layer. In agreement with the findings, caspase-1 deficient mice showed less prominent light damage than wild type mice. Gene therapy by Bcl-xL was effective to protect retinal photoreceptor damage in RCS rats.

Animals↗

Distribution of specific intermediate-filament proteins in the goldfish retina.

The intermediate-filament proteins expressed in the goldfish retina were investigated by immunohistochemistry and by immunoblotting. Polyclonal antibodies that previously had been raised against the goldfish optic nerve neurofilament (ON1 and ON2) and glial filament (ON3 and ON4) proteins were used in this study. Anti-ON1/ON2 antiserum reacted on a retinal immunoblot with two proteins having molecular weights and isoelectric points corresponding to those of ON1 and ON2. Histologically, the most pronounced anti-ON1/ON2 reactivity was observed in the ganglion cell layer of the goldfish retina. The anti-ON3/ON4 antiserum reacted with a single protein on a retinal immunoblot. This protein had a molecular weight and isoelectric point which corresponded to the goldfish optic nerve glial filament proteins. This anti-serum labeled horizontal cells in retina sections. Three previously unidentified goldfish visual-pathway intermediate-filament proteins sharing a molecular weight of 60K were observed on two-dimensional gels of retinal cytoskeletal proteins and on retinal immunoblots which were probed with a monoclonal antibody which recognizes an epitope common to all intermediate filament proteins. The possible existence of homologs of mammalian GFAP and vimentin in the goldfish retina was also explored. Antibodies directed against mammalian GFAP and vimentin labeled the Müller fibers and the cone horizontal cells, respectively. However, immunoblot analysis and a comparison of the two-dimensional gel electrophoresis patterns of goldfish retinal and rat spinal cord cytoskeletal proteins demonstrated a lack of goldfish proteins identical to the mammalian intermediate-filament proteins.

Animals↗

Effect of melatonin agonists and antagonists on horizontal cell spinule formation and dopamine release in a fish retina.

The crucian carp retina was used to study the effects of the melatonin antagonist p697 (N-pentanoyl 2-benzyltryptamine) and the melatonin agonists [+]- and [-]-AMMTC (N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazol e) on horizontal cell spinule formation, an indicator of the state of retinal adaptation. DH97 was capable of both counteracting dark-adaptive spinule degradation and inducing light-adaptive spinule formation at the beginning of the dark phase. Addition of dopamine receptor blockers opposed the action of DH97 on spinules, with SCH 23930, a D1 dopamine receptor antagonist, being more effective than the D2 receptor antagonist sulpiride. DH97 induced a twofold increase in dopamine release. We conclude that melatonin acts as a dark signal within the teleost retina by inhibiting the dopaminergic system. In accordance with this, both enantiomers of AMMTC prevented light-induced spinule formation, and reduced dopamine release to below dark-adaptive baseline levels. We suggest that the suppression of spinule formation by AMMTC may be due to either a direct inhibitory interaction between the melatonin agonist and horizontal cell dopamine D1 receptors, or an inhibitory effect on the activity of the dopamine-releasing interplexiform cells.

Adaptation, Ocular↗

Mapping glutamatergic drive in the vertebrate retina with a channel-permeant organic cation.

Patterns of neuronal excitation in complex populations can be mapped anatomically by activating ionotropic glutamate receptors in the presence of 1-amino-4-guanidobutane (AGB), a channel-permeant guanidinium analogue. Intracellular AGB signals were trapped with conventional glutaraldehyde fixation and were detected by probing registered serial thin sections with anti-AGB and anti-amino acid immunoglobulins, revealing both the accumulated AGB and the characteristic neurochemical signatures of individual cells. In isolated rabbit retina, both glutamate and the ionotropic glutamate receptor agonists alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), kainic acid (KA), and N-methyl-D-aspartic acid (NMDA) activated permeation of AGB into retinal neurons in dose-dependent and pharmacologically specific modes. Horizontal cells and bipolar cells were dominated by AMPA/KA receptor activation with little or no evidence of NMDA receptor involvement. Strong NMDA activation of AGB permeation was restricted to subsets of the amacrine and ganglion cell populations. Threshold agonist doses for the most responsive cell groups (AMPA, 300 nm; KA, 2 microM; NMDA, 63 microm; glutamate, 1 mM) were similar to values obtained from electrophysiological and neurotransmitter release measures. The threshold for activation of AGB permeation by exogenous glutamate was shifted to <200 microM in the presence of the glutamate transporter antagonist dihydrokainate, indicating substantial spatial buffering of extracellular glutamate levels in vitro. Agonist-activated permeation of AGB into neurons persisted under blockades of Na+ -dependent transporters, voltage-activated Ca2+ and Na+ channels, and ionotropic gamma-aminobutyric acid and glycine receptors. Cholinergic agonists evoked no permeation.

Agmatine↗

Morphology and birth dates of horizontal cells in the retina of a marsupial.

Most eutherian (placental) mammals have two horizontal cell types; however, one type only has been seen in rodents. In order to assess whether one type of horizontal cell or two is a basic mammalian feature, we have examined the morphology of horizontal cells in a marsupial, the quokka wallaby, by Golgi staining or horseradish peroxidase labelling. The birth dates of horizontal cells have also been determined by 3H-thymidine/autoradiography. There are two types of horizontal cell in the wallaby retina. One type has no axon and corresponds to the axonless cell in eutherian species; the other has shorter dendrites, an axon, and an axonal arbor, corresponding to the eutherian short-axon cell. As in eutherian mammals, the dendrites of each horizontal cell type lie in the outer plexiform layer (OPL) and contact cones and the axonal arbor of the short-axon cell contacts rods. The dendrites of the axonless cells are long, with an average length of 250 microns, and each cell has one, sometimes two, short, stubby processes, which branch off a dendrite, traverse the inner nuclear layer, and reach the inner plexiform layer. The dendritic field of these cells is elongated, and dendrites show a preferential orientation at right angles to the trajectory of overlying ganglion cell axons. Short-axon cells have a morphology similar to that seen in other species, although the axonal arbor is relatively small. Both types of horizontal cell are generated in the first phase of retinal cell generation.

Animals↗

Vision in the deep sea.

The deep sea is the largest habitat on earth. Its three great faunal environments--the twilight mesopelagic zone, the dark bathypelagic zone and the vast flat expanses of the benthic habitat--are home to a rich fauna of vertebrates and invertebrates. In the mesopelagic zone (150-1000 m), the down-welling daylight creates an extended scene that becomes increasingly dimmer and bluer with depth. The available daylight also originates increasingly from vertically above, and bioluminescent point-source flashes, well contrasted against the dim background daylight, become increasingly visible. In the bathypelagic zone below 1000 m no daylight remains, and the scene becomes entirely dominated by point-like bioluminescence. This changing nature of visual scenes with depth--from extended source to point source--has had a profound effect on the designs of deep-sea eyes, both optically and neurally, a fact that until recently was not fully appreciated. Recent measurements of the sensitivity and spatial resolution of deep-sea eyes--particularly from the camera eyes of fishes and cephalopods and the compound eyes of crustaceans--reveal that ocular designs are well matched to the nature of the visual scene at any given depth. This match between eye design and visual scene is the subject of this review. The greatest variation in eye design is found in the mesopelagic zone, where dim down-welling daylight and bio-luminescent point sources may be visible simultaneously. Some mesopelagic eyes rely on spatial and temporal summation to increase sensitivity to a dim extended scene, while others sacrifice this sensitivity to localise pinpoints of bright bioluminescence. Yet other eyes have retinal regions separately specialised for each type of light. In the bathypelagic zone, eyes generally get smaller and therefore less sensitive to point sources with increasing depth. In fishes, this insensitivity, combined with surprisingly high spatial resolution, is very well adapted to the detection and localisation of point-source bioluminescence at ecologically meaningful distances. At all depths, the eyes of animals active on and over the nutrient-rich sea floor are generally larger than the eyes of pelagic species. In fishes, the retinal ganglion cells are also frequently arranged in a horizontal visual streak, an adaptation for viewing the wide flat horizon of the sea floor, and all animals living there. These and many other aspects of light and vision in the deep sea are reviewed in support of the following conclusion: it is not only the intensity of light at different depths, but also its distribution in space, which has been a major force in the evolution of deep-sea vision.

Adaptation, Physiological↗

Morphological and functional identifications of catfish retinal neurons. I. Classical morphology.

The morphology of the catfish horizontal cells is comparable to that in other fish retinas. The external horizontal cells contact cone receptors and are stellate in shape; the intermediate horizontal cells are even more so and contact rod receptors. The internal horizontal cells constitute the most proximal layer of the inner nuclear layer and may possibly be, in reality, extended processes from the other two horizontal cell types. Bipolar cells resemble those in other teleost retinas: the size and shape of their dendritic tree encompass a continuous spectrum ranging from what is known as the small to the large bipolar cells. The accepted definition of amacrine cells is sufficiently vague to justify our originating a more descriptive and less inferential name for the (axonless) neurons in the inner nuclear layer which radiate processes throughout the inner synaptic layer. These starbust and spaghetti cells vary considerably in the character and extent of their dendritic spread, but correlates exist in other vertebrate retinas. Ganglion cells are found not only in the classical ganglion layer but displaced into the inner nuclear layer as well. Several types can be distinguished on the basis of cell geometry and by the properties of their dendritic tree. Not all of the categorization corresponds with previous descriptions; our findings suggest that some reorganization may be necessary in the accepted classification of cells in the proximal areas of the vertebrate retina. A subtle yet remarkable pattern underlies the entire structure of the catfish retina; there exists a definite gradient of size within a particular class of cells, and of configuration among the subclasses of a specific cell type. It remains to be seen if these morphological spectra bear any functional consequences. The fact that the structure of the catfish retina most closely resembles those of other phylogenetically ancient animals, such as the skate and the dogfish shark, testifies to its primitive organization; morphological and functional mechanisms discernible in this simple system may, therefore, be applicable to the retinas of higher ordered vertebrates.

Animals↗

GABA and glycine modify the balance of rod and cone inputs to horizontal cells in the Xenopus retina.

Under mesopic conditions, the light-evoked waveform of horizontal cells in Xenopus retina reflects synaptic input from both rod and cone photoreceptors. These inputs interact non-linearly: the response to a weak red (cone-effective) flash is increased up to four-fold when the red stimulus falls on a green (rod-effective) background by reference to the response elicited by the same red flash on a dark field. We refer to this phenomenon as enhancement. It was not observed either when stimulus and field wavelengths were reversed or were of the same color. Enhancement was not altered by polarization of the horizontal cell membrane up to +/- 30 mV with extrinsic current. Enhancement could not be elicited with any combination of test and background wavelengths under photopic conditions. Superfusion of the retina with GABA resulted in a hyperpolarization of the horizontal cell membrane and an emphasis of the rod input to the horizontal cell light-evoked response. Picrotoxin depolarized the cell and favored the cone input. Enhancement was altered in predictable ways by these drugs. Glycine reduced selectively the cone input to the horizontal cell, whereas its antagonist, strychnine, increased the rod input. The results are interpreted to indicate that the excitability of the horizontal cell is modified both by distal and proximal retinal circuits; a glycinergic interplexiform cell probably plays a role in the latter pathway.

Animals↗

The intermediate filament complement of the retina: a comparison between different mammalian species.

We compared the intermediate filament expression of the various cell types in the fully differentiated neural retina from rat, mouse, rabbit, guinea pig, cow, pig, and cat. Many cell types had an intermediate filament complement conserved across species boundaries, such as Müller cells and retinal ganglion cells. In some species (rabbit, guinea pig, and cow), however, we were unable to visualize GFA (glial fibrillary acidic)-positive retinal astrocytes, although such profiles were clearly visible in the remainder. Horizontal cell staining proved to be extremely species-variable. In rat and mouse the processes of these cells were identically displayed with antibodies to vimentin and all three neurofilament triplet proteins. In cow they decorated with antibodies to vimentin and antibodies to the two lower molecular weight neurofilament proteins alone, whereas in pig, rabbit and guinea pig all three neurofilament proteins but not vimentin were present. Finally cat horizontal cells stained for all three neurofilament proteins, some finer processes being additionally stainable with vimentin. A further surprise was the visualization of profiles positive only for the two lower molecular weight neurofilament proteins in the inner nuclear layer of both rabbit and guinea pig retina but not the other species. The implications of these results will be discussed.

Animals↗