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PubMed1981

The distribution of ganglion cells in the retina of the North American opossum (Didelphis virginiana).

The distribution of ganglion cells in the retina of the opossum was determined from whole-mounted retinae stained with cresyl violet. Isodensity lines were approximately circular with a peak density of 2,000 to 2,700 cells/mm2 in superior temporal retina (area centralis). The total number of retinal ganglion cells was estimated to be 72,000 to 135,000 (mean 101,026) in retinae ranging from 125 to 187 mm2 in total area. Three groups of ganglion cells were distinguished on the basis of soma size and retinal topography. Large cells (24 to 32 micrometer diameter) were fairly evenly distributed across the retina. Medium cells (12 to 23 micrometer diameter) were more numerous in the superior temporal quadrant than in other regions of the retina. Small cells (7 to 11 micrometer diameter) were prominent in all retinal regions, but particularly in nasal and inferior retina. An analysis of topographical differences in soma size distribution suggests that the medium size cells can be further subdivided into small-medium and large-medium groups.

Animals↗
PubMed1981

Freeze-fracture study of photoreceptor outer segments and pigment epithelium in dystrophic and normal retinas.

The intramembrane organization of outer segment (OS) membranes and pigment epithelial (PE) microvilli has been studied in rats (10-17 postnatal days) with inherited retinal degeneration (RCS) and in normal retinas from genetically controlled rats (RCS-rdy+). The OS plasma membranes of both dystrophic and normal retinas are characterized by large particles surrounding circular, particle-free zones on the P-faces (cytoplasmic leaflets) and a sparse distribution of particles on the E-faces (external leaflets). No regional differences in particle distribution are observed in either basal or distal plasma membrane regions. Outer segment disc membranes are characterized by large, densely packed P-face particles and ridged E-faces with very few particles. Small, particle-free patches of membrane are present in the basal disc P-faces of both normal and dystrophic retinas, which Andrews and Cohen ("79) have described as characteristic of newly added disc membrane. In dystrophic retinas, larger, particle-free domains are observed in the distal disc membranes (P-faces) and accumulating membranous debris. In older retinas, which have accumulated more debris, the particle-free domains occupy vast areas of the membrane faces and it is not possible to identify these membranes as belonging to either discs of plasma membranes. No comparable areas of particle-free membrane are observed in the distal discs and OS plasma membranes of normal retinas. Pigment epithelial microvillus membranes are characterized by an intermixture of large and medium-sized particles surrounding irregular particle-free areas, but no differences between normal and dystrophic PE membranes are observed. The changes in particle distribution observed in the dystrophic retinas suggests that the intramembrane molecular composition of older disc membranes has become altered or rearranged as the OS membranes accumulate as debris.

Aging↗
PubMed1984

Development and degeneration of retina in rds mutant mice: electron microscopy.

In the retina of mice homozygous for the retinal degeneration slow (rds) gene, receptor outer segments failed to develop and typical disc structures were never observed. However, cilia surrounded by a plasma membrane were regularly present. At the time when outer segments grew in the normal retina, the optic ventricle in the mutant showed an accumulation of membrane-bound vesicles of varying size and density. The vesicles declined in frequency at later stages of degeneration. After initial growth, the inner segments in the mutant retina remained stunted but maintained their morphological differentiation, including the ciliary structures. Their number declined with loss of visual cells. In the mutant retina development of synapses, between the receptor cells and the processes of the horizontal cells and the bipolar cell dendrites, followed in normal sequence. Formation of spherule terminals of the rods, with one triad synapse, and of pedicle terminals of the cones, with multiple triad synapses, was recorded in the same way as in the normal retina. With loss of visual cells in the mutant retina, some of the profiles of the surviving spherule terminals showed an increased occurrence of two, three, or more synaptic sites. This growth resulted from enlargement and branching of the ribbons and sprouting from the postsynaptic elements. Similar changes were not observed in the pedicle terminals. The pigment epithelial cells in the mutant mice appeared initially normal, but phagolysosomal structures were absent. However, various inclusion bodies appeared within the pigment epithelial cells following degenerative changes in the retina. In some places, the basal infoldings deepened their furrows while thinning the cytoplasmic part of the epithelium. Failure to form the outer segments and the subsequent lysis of the visual cells appear to be the primary effects of the rds gene, whereas the synaptic growth in the sperule terminals and the changes in the pigment epithelium appear to be consequential to those defects.

Animals↗
PubMed1984

Non-uniform postnatal growth of the cat retina.

The distributions of alpha-type ganglion cells in 3-week-old and adult cats were used to measure the increase in the distances between existing cells and thus the amount of growth in various regions of the retina. Growth shows two major non-uniformities. (1) The area centralis is at the point of minimum growth; its area increases by only about 3% while regions near the retinal margin increase in area by about 80%. (2) The retina grows about half as much in linear extent as does the radius of the eye and thus comes to occupy a smaller fraction of the globe. Measurements of retinal dimensions indicate that both non-uniformities also occur from birth to 3 weeks. These non-uniformities have the following implications. (1) They would tend to elongate dendritic fields radially, in the direction of the area centralis, in central retina but perpendicular to this direction in peripheral retina. However, these asymmetries are probably not the primary reason why ganglion cells throughout the retina tend to have radially oriented dendritic fields (Leventhal and Schall, '83). (2) Greater growth in the periphery could contribute to the gradient of increasing dendritic field size from central to peripheral retina if the dendritic fields of ganglion cells passively stretched as the retina expanded. Passive stretching is not the primary determinant of dendritic extent, however, because the dendritic fields of beta-type ganglion cells were found to grow 70% more from 3 weeks to adulthood than can be accounted for by passive stretching. (3) Greater peripheral growth steepens the central-to-peripheral gradient of decreasing ganglion cell density; if this trend also occurs prenatally, it could be the major factor in producing the final adult gradient.

Animals↗
PubMed1987

Relationship between astrocytes, ganglion cells and vasculature of the retina.

We have studied the distribution of astrocytes in the ganglion cell and nerve fibre layers of the retina in cat, rat, rabbit, and possum using anti-serum and a monoclonal antibody against glial fibrillary acidic protein (GFAP) and our own monoclonal antibody against glial filaments. The distribution of retinal astrocytes appears to be strongly determined by the vasculature of the retina; astrocytes are absent from almost all the retina of the possum and from the avascular regions of the rabbit retina. In the cat and rabbit, retinal astrocytes also show a strong affinity for the bundles of ganglion cell axons found at the inner surface of the retina. Retinal astrocytes do not invest the somas of ganglion cells, and even in areas of retina in which they are numerous, they are sharply confined to the layer of ganglion cell axons. It is suggested that retinal astrocytes are "immigrant" fibrous astrocytes that enter the retina with its vasculature.

Animals↗
PubMed1988

Cotransplantation of embryonic mouse retina with tectum, diencephalon, or cortex to neonatal rat cortex.

Retinae from embryonic mice were transplanted to the occipital cortex of neonatal rats together with their normal target regions, tectum or diencephalon, from embryonic mice or rats. In control experiments, retinae were cotransplanted with embryonic rat occipital cortex. In over 80% of the experimental animals, both transplants differentiated and grew. Ganglion cells in the retinae cotransplanted close to tectum or diencephalon survived for at least 15 weeks. Their survival was associated with the development of a distinct optic fiber layer and outgrowth of axons from the transplanted mouse retina. Specific innervation of distinct patches within the cotransplanted rat tectum or diencephalon was demonstrated by the use of an anti-mouse antibody. The innervated regions, which could be as far away as 1.3 mm from the retinae, were correlated with cytological features of the cotransplanted tectum or diencephalon. By contrast, the host cortex was never innervated by the transplanted retinae. In the control animals in which the retinae were cotransplanted with occipital cortex and in four animals in which the cotransplants lay more than 2.7 mm apart, no ganglion cells were identified and there was no evidence of an optic fiber layer, outgrowth of axons, or innervation. These results support the idea that in order to survive, retinal ganglion cells need to innervate an appropriate target region. Further, the specific innervation of regions within the cotransplanted tectum or diencephalon suggests that these target regions are able to exert a tropic influence on the axons of retinal ganglion cells, even in the absence of many of the normal structure cues.

Animals↗
PubMed1989

Gap junction particle density of horizontal cells in goldfish retinas lesioned with 6-OHDA.

The I1 dopaminergic interplexiform cells of the fish retina are believed to modulate horizontal cell coupling by increasing gap junction resistance. Dopamine also modulates the morphology of horizontal cell gap junctions and mimics the effects of light adaptation. To determine whether the light-dependent changes in gap junction morphology are due to endogenous dopamine release, horizontal cell gap junctions were studied in goldfish retinas lacking dopaminergic neurons. Dopaminergic interplexiform cells were destroyed by intraocular injections of 6-hydroxydopamine in both eyes. After lesioning, fish were treated in one of four ways: (1) light-adapted, (2) dark-adapted (1 hour), (3) light-adapted and given an intraocular injection of dopamine, or (4) dark-adapted (1 hour) and injected with dopamine. The effectiveness of lesioning was evaluated by autoradiographic detection of [3H]-dopamine uptake in the retina of one eye. Retinas in which lesioning of the contralateral eye was deemed effective were processed for freeze-fracture electron microscopy and the particle density of horizontal cell gap junctions determined. Lesioned retinas, whether light- or dark-adapted, had elevated horizontal cell soma gap junction particle densities compared to lesioned retinas treated with dopamine. These results demonstrate that high soma gap junction particle densities can be correlated with the absence of dopamine and low densities associated with the presence of dopamine. The differences in gap junction particle density between lesioned and lesioned + dopamine-treatment were similar to differences between nonlesioned dark-adapted (1 hour) and light-adapted retinas, respectively. Therefore, the particle density of light- and dark-adapted soma gap junctions suggests a greater release of dopamine in light-adapted fish than in 1 hour dark-adapted fish.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2004

Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation.

Three retinaldehyde dehydrogenase genes (Raldh1, Raldh2, and Raldh3) expressed in unique spatiotemporal patterns may control synthesis of retinoic acid (RA) needed for retina development. However, previous studies indicate that retina formation still proceeds normally in Raldh1-/- mouse embryos lacking RA synthesis in the dorsal neural retina at the optic cup stage. Here, we demonstrate that Raldh2-/- embryos lacking RA synthesis in the optic vesicle exhibit a failure in retina invagination needed to develop an optic cup. This was also observed in Raldh1-/-:Raldh2-/- double mutants, which develop similarly. Both mutants retain RA activity in the lens placode associated with Raldh3 expression, but this RA activity is insufficient to induce optic cup formation. Maternal RA administration at the optic vesicle stage rescues optic cup formation in Raldh2-/- and Raldh1-/-:Raldh2-/- embryos, demonstrating that Raldh1 is not required during rescue of optic cup development. The optic cup of rescued Raldh1-/-:Raldh2-/- embryos exhibits normal RA activity and this is associated with Raldh3 expression in the retina and lens. Thus, RA signaling initiates in the optic vesicle in response to Raldh2 but can be maintained during optic cup formation by a gene other than Raldh1, most likely Raldh3. Loss of optic vesicle RA signaling does not effect expression of early determinants of retina at the optic vesicle stage (Pax6, Six3, Rx, Mitf). Our findings suggest that RA functions as one of the signals needed for invagination of the retina to generate an optic cup.

Aldehyde Oxidoreductases↗
PubMed1995

Gap junctions in the vertebrate retina.

The vertebrate retina is a highly laminated assemblage of specialized neuronal types, many of which are coupled by gap junctions. With one interesting exception, gap junctions are not directly responsible for the 'vertical' transmission of visual information from photoreceptors through bipolar and ganglion cells to the brain. Instead, they mediate 'lateral' connections, coupling neurons of a single type or subtype into an extended, regular array or mosaic in the plane of the retina. Such mosaics have been studied by several microscopic techniques, but new evidence for their coupled nature has recently been obtained by intracellular injection of biotinylated tracers, which can pass through gap junctional assemblies that do not pass Lucifer Yellow. This evidence adds momentum to an existing paradigm shift towards a population-based view of the retina, which can now be envisaged both as an array of semi-autonomous vertical processing modules, each extending right through the retina, and as a multi-layered stack of interacting planar mosaics, bearing some resemblance to a set of interleaved neural networks. Junctional conductance across mosaics of horizontal cells is known to be controlled dynamically with a circadian rhythm, and other dynamically-regulated conductance changes are also likely to make important contributions to signal processing. The retina is an excellent system in which to study such changes because many aspects of its structure and function are already well understood. In this review, we summarize the microscopic appearance, coupling properties and functions of gap junctions for each cell type of the neural retina, the regulatory properties that could be provided by selective expression of different connexin proteins, and the evidence for gap junctional coupling in retina development.

Animals↗
PubMed1975

Regeneration of the retina in the adult newt, Triturus cristatus, following surgical division of the eye by a limbal incision.

The regeneration of a retina in adult Triturus cristatus, following surgical division of the eye by a limbal incision, was studied. In agreement with recent reports, it was found that the regenerating retina is dervied from two sources; the retinal pigment epithelium and the pars ciliaris retinae. However, following a limbal incision, most of the retina appears to be derived from the retinal pigment epithelium in the posterior part of the eye. An unexpected finding of this study was that large cystlike spaces form in the fundal regions of the eye, between the regenerating retina and the retinalpigment epithelium. These spaces appear between five and eight days post-operative and persist long enough (25 to 30 days postoperative) to disrupt the fundal portion of the rengenerating retina and to cause it to lag behind the rest of the regenerate, in its development. The relationship of these observations to the genesis of positional markers in the regenerating retina is discussed.

Animals↗
PubMed1990

On the duplex nature of the skate retina.

The skate retina contains only one type of photoreceptor which has rod-like properties in the dark-adapted state. In the presence of background illumination, the receptors take on cone-like properties, i.e., their photoresponses become much faster, are less sensitive to light, and can be elicited in the presence of very bright backgrounds. Although the transformation is an extremely slow process, the skate retina performs like that of animals with mixed, rod-cone retinae. In this report we examine some postreceptoral features which may relate to this remarkable behavior. We show, for example, that the skate photoreceptor terminals make two kinds of junctions (ribbon synapses and basal junctions) that appear analogous to the two kinds of synaptic contacts made by cone terminals in other species. Furthermore, two types of horizontal cells are seen in the skate retina. Although the light-evoked responses of these horizontal cells are similar, there are differences in their current profiles recorded under voltage clamp, and in the nature of their dendritic processes. We have also observed several unusual postreceptoral structural features that may have some bearing on the response properties of the skate retina. In addition, a comparison of the adaptive properties of the receptor potential with those of intraretinal responses (b-wave, PNR) reveals differences that suggest strongly the presence of a network adaptive mechanism originating within the proximal retina. The network mechanism appears to be controlled to a large extent by the extracellular concentration of potassium [K+]0; i.e., changes in [K+]0 affect significantly the sensitivities of the b-wave and PBR, but have little effect on responses arising in the distal retina.

Adaptation, Ocular↗
PubMed1990

Development of A1 adenosine receptors in the chick embryo retina.

Adenosine inhibits cyclic AMP synthesis induced by dopamine in embryonic but not in post-hatched chick retinas. N6-Cyclohexyladenosine (CHA), which preferentially activates A1 receptors as well as 2-chloroadenosine, inhibits cyclic AMP accumulation induced by dopamine in retinas from 10-day-old embryos (E10) with IC50's of 0.1 and 0.5 microM, respectively, but this effect is not detectable after hatching. In order to verify if this developmental change reflects variations in the number or affinity of A1 adenosine receptors, their development during chick retina ontogeny was studied. Binding studies using 3(H)CHA revealed the presence of A1 receptors at all stages of development examined, including the post-hatched retina. The number of binding sites increased between E10 and E17, and then decreased in post-hatched animals. In the latter, 3(H)CHA binding was to a single site with a Bmax of 128.6 +/- 13.4 fmol/mg protein and a Kd of 2.1 + 0.2 nM. Various ligands showed similar hierarchies of affinity for the A1 receptor in embryonic and post-hatched retinas, namely, CHA greater than R-N6-phenylisopropyladenosine (1-PIA) greater than 5'-N-ethylcarboxamideadenosine (NECA) greater than isobuthylemethyl-xanthine (IBMX). Given that CHA inhibited forskolin-induced cyclic AMP production and Gpp(NH)p inhibited 3(H)CHA binding in both embryonic and post-hatched retinas, it appears that receptor coupling to adenylate cyclase is present since early embryonic stages. The results suggest that the A1 receptors may have different functions in the embryonic as compared to the mature chick retina.

Adenosine↗
PubMed2004

Large-scale identification and characterization of genes with asymmetric expression patterns in the developing chick retina.

To understand the molecular basis of topographic retinotectal projection, an overall view of the asymmetrically expressed molecules in the developing retina is needed. We performed a large-scale screening using restriction landmark cDNA scanning (RLCS) in the embryonic day 8 (E8) chick retina. RLCS is a cDNA display system, in which a large number of cDNA species are displayed as two-dimensional spots with intensities reflecting their expression levels as mRNA. We searched for spots that gave different signal intensities between the nasal and temporal retinas or between the dorsal and ventral retinas, and detected about 200 spots that were preferential on one side in the retina. The asymmetric expression of each gene was verified by Northern blotting and in situ hybridization. By subsequent analyses using molecular cloning, DNA sequencing, and database searching, 33 asymmetric molecules along the nasotemporal (N-T) axis and 20 along the dorsoventral (D-V) axis were identified. These included transcription factors, secretory factors, transmembrane proteins, and intracellular proteins with various putative functions. Their expression profiles revealed by in situ hybridization are highly diverse and individual. Moreover, many of them begin to be expressed in the retina from the early developmental stages, suggesting that they are implicated in the establishment and maintenance of regional specificity in the developing retina. The molecular repertoire revealed by this work will provide candidates for future studies to elucidate the molecular mechanisms of topographic retinotectal map formation.

Animals↗
PubMed1982

Swelling of the Müller fibers in the chicken retina.

A high potassium concentration (33 meq) in the solution superfusing the isolated chicken retina causes an increase in the tissue transparency. An L-glutamate (1 mM) or L-proline (10 mM) solution has the same effect. Swelling of the Müller fibers, which have a radial position in the retina, could explain the transparency increase. This possibility was investigated in electron micrographs of retinas subjected to these treatments and fixed by freeze-substitution to preserve the water distribution in the tissue. The Müller fibers in the controls had a mean diameter of 0.22 micrometer. The fibers in retinas bathed for 2 min in the high [K+] solution were more than three times as thick (0.74 micrometer); the fibers in glutamate-treated retinas were more than twice as thick (0.49 micrometer). The fibers in the proline-treated retinas had a diameter of 0.39 micrometer. The glutamate- and proline-induced swelling may be due to a K+ release from neuronal elements, acting on the Müller fibers. The fiber swelling was postulated to be the expression of different Donnan equilibriums of fibers bathed in solutions of different K+ concentrations. The observed swelling caused by the high [K+] solution was compared with the theoretical swelling of the fiber as an ideal Donnan system, postulating permeabilities for different ions of the fiber membrane. This suggested that the high [K+] solution causes an increase in Na+ permeability in addition to the permeability of the membrane for K+, Cl-, and HCO3-. Chemical fixation with glutaraldehyde and formaldehyde in an Na-phosphate buffer yielded micrographs in which the Müller fibers of retinas treated with a high [K+] or a glutamate solution had diameters similar to those of the control preparations.

Animals↗
PubMed1993

Immunocytochemical identification of serotonin-synthesizing neurons in the vertebrate retina: a comparative study.

Serotonin-synthesizing neurons in the retinas of goldfish, axolotl, turtle, chick, rabbit and cat were identified using double labelling with anti-serotonin and anti-phenylalanine hydroxylase antibodies. The latter antibody recognizes tryptophan 5-hydroxylase, one of the synthesizing enzymes for serotonin. Neurons labelled by both markers were considered to be serotonin-synthesizing neurons, while those only with serotonin-immunoreactivity were assumed to be serotonin-accumulating neurons. In the goldfish and chick retinas, all serotonin-immunoreactive amacrine cells (S1) were positive for phenylalanine hydroxylase. In the axolotl and turtle retinas, all the S1 amacrine cells, and only 52.8% and 40.5% of S2 amacrine cells were double-labelled. Although serotonin-immunoreactive bipolar cells were observed in the turtle and chick retinas, the synthesizing enzyme for serotonin could not be detected in these cells. In the rabbit and cat retinas, tryptophan hydroxylase could not be revealed in any cell type with immunocytochemistry. In control experiments SLI neurons in the raphe nuclei of the brain stem always exhibited PH-LI in all species examined, including mammals, indicating that our anti-PH antibody is able to recognize tryptophan hydroxylase across vertebrate classes. These results indicate that the majority of serotonin-immunoreactive amacrine cells are able to synthesize serotonin and are the source of endogenous serotonin in the non-mammalian retina, while some serotonin-immunoreactive amacrine and bipolar cells possibly only accumulate serotonin. We also suggest that serotonin may not be a primary neurotransmitter in the serotonin-accumulating bipolar and amacrine cells of the non-mammalian retina.

Ambystoma mexicanum↗
PubMed1993

Horizontal cells of the normal and dystrophic rat retina: a wholemount study using immunolabelling for the 28-kDa calcium-binding protein.

Immunocytochemistry with a monoclonal antibody against the 28-kDa calcium-binding protein (28-kDa CaBP) was used to study horizontal cells in both congenic control (RCS-rdy+) and dystrophic (RCS) 3-month-old rat retina. We found that horizontal cells in the RCS-rdy+ rat retinas were distributed evenly from the centre to the peripheral retina with a mean density of 783 cells mm-2. Cell size ranged between 6.5-12.5 microns in diameter with a mean of 8.87 microns. Individual cell processes could not be followed readily, however they formed a narrow plexus within the outer plexiform layer with the primary dendrites extending radially from each cell soma in an organized manner. In the RCS rat, by contrast, the horizontal cell processes were more disorganized than in the congenic controls. The degree of disorganization varied across the retina. In the posterior pole, where all outer layers had been lost, many processes were grossly swollen along their length and at the tips. The cell somas were also distributed more widely in the depth of the retina. In the peripheral retina, where a debris layer was still present, the processes were less swollen but they extended abnormally widely in depth. Despite the disorganized structure the mean and range of cell size (9.23 microns, 5.5-15.5 microns), and cell density (796 cells mm-2) were similar to that of the control RCS-rdy+ animals. These findings indicate that in dystrophic retinas beyond a certain stage of degeneration the horizontal cells become abnormal in their structure but are present at a normal density and the somas are not grossly swollen or shrunken.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Multiple kinesin family members expressed in teleost retina and RPE include a novel C-terminal kinesin.

Kinesins comprise a large superfamily of microtubule-based motor proteins, individual members of which mediate specific types of motile processes. To identify kinesin family members (KIFs) that are critical to retinal function and thus to vision, a reverse transcriptase polymerase chain reaction (RT-PCR) cloning strategy was used to isolate putative KIFs expressed in the neural retina and retinal pigmented epithelium (RPE) of the striped bass, Morone saxatilus. Eleven fish KIFs (FKIFs) were isolated from neural retina and six of the same FKIFs were also isolated from RPE. One of the KIFs identified in this screen, FKIF2, was the most prevalent clone detected both in the retina (41% of clones) and RPE (72% of clones). Based on predicted amino acid sequence homology within the motor domain, seven of the FKIFs have been tentatively assigned to known kinesin families: the kinesin heavy chain family (FKIF1, 5 and 9), the unc104/KIF1 family (FKIF3 and 8), the KIF2 family (FKIF4), and the cKIF family (FKIF2). Northern blot analysis revealed that each detectable FKIF exhibited a unique tissue-specific expression pattern. Since FKIF2 was more highly expressed in retina than in any other tissue tested, including brain, and was the most abundant KIF message expressed in both retina and RPE, it was examined in more detail and the complete approximately 2.3 kb open reading frame for FKIF2 was cloned and sequenced. The predicted amino acid sequence indicates that FKIF2 has a C-terminal motor domain, and thus is a member of the cKIF family. FKIF2 is only 36.5% identical at the amino acid level to the most closely related cKIF in the database, suggesting that FKIF2 may be a novel member of this family. Antibodies raised against a unique peptide specific to FKIF2 recognize an approximately 80 kd protein in homogenates of retina, RPE, brain and kidney. The pronounced expression of FKIF2 in retina and RPE suggests that FKIF2 may play an important role in microtubule-dependent motile events in these two tissues.

Amino Acid Sequence↗
PubMed1998

Age-related changes in the tiger salamander retina.

Tiger salamanders have been used in visual science because of the large size of their cells and the ease of preparation and maintenance of in vitro retinal preparations. We have found that salamanders over 27 cm in length show a variety of visual abnormalities. Compared to smaller animals (15-23 cm), large animals exhibited a decrease in visual responses determined by tests of the optomotor reflex. Small animals responded correctly an average of 84.5% of the time in visual testing at three light levels compared to an average of 68.4% for the large animals with the poorest visual performance at the lowest level of illumination. In addition, large animals contained (i) histological degeneration of the outer retina, in particular, loss and disruption of outer segments and abnormalities of the retinal pigmented epithelium, (ii) loss of cells, including photoreceptors, by apoptosis as evaluated with the TUNEL technique, and (iii) an increase in the number of macrophages and lymphocytes within the retina as determined by morphological examination. These histological changes were present in all large animals and all quadrants of their retinas. In contrast, small animals showed virtually no retinal degeneration, no TUNEL-positive cells, and few immune-like cells in the retina. Since large animals are also older animals. the visual changes are age-related. Loss of visual function and histological degeneration in the outer retina also typify aged human eyes. Thus, we propose that large salamanders serve as an animal model for age-related retinal degeneration. In addition to providing a source of aging retina that is readily accessible to experimental manipulation, the salamander provides a pigmented retina with a mixed (2:1, rod:cone) population of photoreceptors, similar to the degeneration-prone parafoveal region of the human eye.

Aging↗