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PubMed2005

Intraretinal oxygen distribution in the monkey retina and the response to systemic hyperoxia.

PURPOSE: To measure the intraretinal oxygen distribution and consumption in the fovea, the parafovea, and the inferior retina in the monkey eye and determine the influence of graded systemic hyperoxia. METHODS: Oxygen sensitive microelectrodes were used to measure the oxygen tension as a function of depth through the retina in anesthetized monkeys (n = 8) under normoxic and hyperoxic conditions. Oxygen consumption rates in the avascular regions of retina were determined by fitting the oxygen profiles to established oxygen consumption models. RESULTS: Under normoxic conditions, in the foveal area, the intraretinal oxygen distribution reflected the absence of retinal capillaries and the predominantly choroidal origin of retinal oxygenation. A similar shape of oxygen distribution was seen in the parafoveal retina with the addition of local perturbations in the inner retina attributed to the presence of retinal capillaries. In the inferior retina the same general shape was found. Oxygen consumption in the outer retina was higher in the parafoveal region, and the minimum oxygen tension was lower. During hyperoxia, choroidal oxygen levels in all areas increased dramatically, but the increase in oxygen tension in the inner retina was much less. The avascular nature of the foveal area allowed oxygen consumption analysis of both the inner and outer retina and showed that inner retinal oxygen consumption increased significantly during hyperoxic ventilation to a level equivalent to that of the outer retina. CONCLUSIONS: In the outer retina of the monkey the P(O2) minimum is lower, and the oxygen consumption rate is higher in the parafoveal region. During systemic hyperoxia, outer retinal oxygen consumption is unaffected, but in the foveal area, total oxygen consumption increases. This regulation of oxygen consumption in the monkey retina is comparable to that reported in lower mammals and may represent an important mechanism in retinal homeostasis.

Animals↗
PubMed1995

Axonal guidance in the chicken retina.

During retina development, ganglion cells extend their axons exclusively into the innermost tissue layer, but not into outer retina layers. In order to elucidate guiding mechanisms for axons, tissue strips of embryonic chicken retinae were explanted onto retinal cryosections (cryoculture). Ganglion cell axons originating from the explant grew preferentially on the innermost retina layer of cryosections, whereas outer tissue layers were avoided, very much as in vivo. Stereotropism, interaction with laminin of the basal lamina and axonal fasciculation did not significantly affect oriented axonal outgrowth, so that stereotropism as a guidance mechanism could be excluded. Ganglion cell axons were not directed by physical barriers, e.g. microstructured silicon oxide chips. Similarly, UV induced protein inactivation revealed that laminin present in the inner retina did not provide a guidance cue. Even in the absence of ganglion cell axons in retinal cryosections due to prior optic nerve transection in ovo, the growth preference for the innermost retina layer was maintained in cryocultures. However, oriented elongation of axons along the innermost retina layer was lost when radial glial endfeet were selectively eliminated in retinal cryosections. In addition, glial endfeet provided an excellent growth substratum when pure preparations of endfeet were employed in explant cultures. The preference for glial endfeet positioned at the inner retina surface was accompanied by the avoidance of outer retina layers, most likely because of inhibitory components in this region. This assumption is corroborated by the finding that addition of exogenous growth-promoting laminin to cryosections did not abolish the inhibition. Laminin on glass surfaces provided an excellent substratum. Axonal outgrowth was also seriously hampered on specifically purified cells of the outer retina. Most notable, however, in cryocultures aberrant innervation of outer retina layers could be induced by prior heat or protease treatment of cryosections, which pointed to proteins as potential inhibitory components. In summary the data substantiate the hypothesis that within the retina, ganglion cell axons are guided by a dual mechanism based on a permissive and an inhibitory zone. Radial glia is likely to be instructive in this process.

Animals↗
PubMed2004

Altered expression of genes of the Bmp/Smad and Wnt/calcium signaling pathways in the cone-only Nrl-/- mouse retina, revealed by gene profiling using custom cDNA microarrays.

Many mammalian retinas are rod-dominant, and hence our knowledge of cone photoreceptor biology is relatively limited. To gain insights into the molecular differences between rods and cones, we compared the gene expression profile of the rod-dominated retina of wild type mouse with that of the cone-only retina of Nrl(-/-) (Neural retina leucine zipper knockout) mouse. Our analysis, using custom microarrays of eye-expressed genes, provided equivalent data using either direct or reference-based experimental designs, confirmed differential expression of rod- and cone-specific genes in the Nrl(-/-) retina and identified novel genes that could serve as candidates for retinopathies or for functional studies. In addition, we detected altered expression of several genes that encode cell signaling or structural proteins. Prompted by these findings, additional real-time PCR analysis revealed that genes belonging to the Bmp/Smad and Wnt/Ca(2+) signaling pathways are expressed in the mature wild type retina and that their expression is significantly altered in the Nrl(-/-) retina. Chromatin immunoprecipitation analysis of adult retina identified Bmp4 and Smad4, which are down-regulated in the Nrl(-/-) retina, as possible direct transcriptional targets of Nrl. Consistent with these studies, Bmp4 and Smad4 are expressed in the mature rod photoreceptors of mouse retina. Modulation of Bmp4 and/or Smad4 by Nrl may provide a mechanism for integrating diverse cell signaling networks in rods. We hypothesize that Bmp/Smad and Wnt/Ca(2+) pathways participate in cell-cell communication in the mature retina, and expression changes observed in the Nrl(-/-) retina reflect their biased utilization in rod versus cone homeostasis.

Animals↗
PubMed1989

(Na+ + K+)-ATPase and opsin in retinas of RCS dystrophic rats: time course study.

Retinas of Royal College of Surgeons (RCS) dystrophic rats were investigated immunocytochemically for the distribution of the membrane-bound enzyme (Na+ + K+)-ATPase and the photo-pigment opsin prior to and during the retinal disease process. Retinas of 11 day-old dystrophic and control Long Evans rats showed (Na+ + K+)-ATPase immunostain most dense in the outer nuclear layer (ONL) and inner plexiform layer (IPL). Also, in these retinas, immunostaining for opsin was dense along rod inner segments (RIS) and on plasmalemma of ONL cell bodies and several cell bodies in the inner nuclear layer (INL). In retinas of control rats at 30 days and later, less dense (Na+ + K+)-ATPase immunostain was detected in the ONL than at 11 days and opsin-immunostained ROS were also detected. However, (Na+ + K+)-ATPase immunostained RIS were shorter in retinas of 30 day-old dystrophic than in retinas of age-matched control rats and an opsin-immunostained debris zone was also observed in dystrophic retinas. In retinas of 60 day-old dystrophic rats, the opsin-immunostained debris zone was more prominent than at 30 days, while the few ONL cell bodies immunostained for both proteins. Also, the outer IPL of 60 day-old dystrophic rat retinas immunostained more densely for (Na+ + K+)-ATPase than the inner IPL. In 120 day-old dystrophic rat retinas, (Na+ + K+)-ATPase immunostain was detected in the INL and IPL, while opsin staining was demonstrated only in the debris zone. This opsin-immunostained debris disappeared in a central-to-peripheral gradient. (Na+ + K+)-ATPase immunostain was still present in the INL and IPL in retinas and the optic nerve of one year-old RCS dystrophic rats; however, opsin was restricted to a few surviving cell bodies in the peripheral retina.

Animals↗
PubMed1987

Somatostatin-like immunoreactive material in the rabbit retina: immunohistochemical staining using monoclonal antibodies.

Two mouse monoclonal antibodies to somatostatin-14 were used with avidin-biotin-peroxidase immunohistochemical technique to examine the rabbit retina. In agreement with a previous study using a polyclonal anti-serum, a sparse population (about 1,000 per retina) of neurons in the ganglion cell layer are immunoreactive for somatostatin; the vast majority of these cells are inferior to the myelinated fiber bundle. In addition, the monoclonal antibodies disclose a second neuronal population that forms a circumferential band of immunoreactive neurons around the extreme periphery of the retina. The cells in the body of the inferior retina have dendrites that ramify in the inner plexiform layer. Both the circumferential band of cells and the cells in the body of the inferior retina give off axonlike processes that run in the inner plexiform layer and do not enter the optic nerve. These long, straight varicose fibers form a meshwork that covers the entire retina. The superior retina, which contains only rare immunoreactive cell bodies, has a plexus of stained fibers comparable to that of the inferior retina. The circumferential band of cells is relatively resistant to the neurotoxin kainic acid, explaining a previously reported observation that this toxin depletes only about 50% of the content of somatostatin-like immunoreactivity from the rabbit retina. Moreover, the somatostatin immunoreactive neurons are not labeled by the intraocular injection of the fluorescent dye DAPI, which labels the cholinergic displaced amacrine cells of the rabbit retina. These observations imply that somatostatin-like immunoreactivity is localized to two populations of associational ganglion cells, neurons with cell bodies in the ganglion cell layer, the axons of which remain within the retina.

Animals↗
PubMed1990

Immunolocalization of cellular retinoic acid binding protein to Müller cells and/or a subpopulation of GABA-positive amacrine cells in retinas of different species.

Retinoic acid (RA) and its specific binding protein, cellular RA binding protein (CRABP), are found in relative abundance in bovine and rat retinas. Since RA does not participate in the visual cycle, the presence of RA and its binding protein in retina suggests that they may be involved in other aspects of retinoid action. As an initial step in identifying the role of RA and its binding protein in retina, monoclonal antibodies were prepared against CRABP purified from bovine retina and used to localize this antigen by immunocytochemistry in retinas of different species. Human and monkey retinas showed specific cytoplasmic labeling of Müller cells. Cat, bovine, rabbit, rat, turtle, and chick retinas showed specific cytoplasmic labeling of some somata in the inner nuclear and ganglion cell layers and characteristic strata in the inner plexiform layer. Cat and bovine retinas also showed cytoplasmic labeling of Müller cells. Immunoreactivity in these species was absent with nonimmune serum or abolished when the antibodies were preabsorbed with purified antigen. Chameleon, goldfish, and frog retinas were nonreactive. We used double-labeling immunofluorescence experiments to determine if the CRABP-positive cells were also positive for known neurotransmitters or associated enzymes. CRABP-positive amacrine cells of cat, cow, rabbit, rat, and chick represented a subset of the more numerous gamma-aminobutyric acid (GABA)-positive amacrine cells. However, turtle CRABP-positive amacrine cells were negative for GABA despite the fact that turtle retina contains many GABA positive cells. CRABP-positive amacrine cells in rat retinas were not immunoreactive for glycine, choline acetyltransferase, somatostatin, or tyrosine hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The morphology and distribution of photoreceptors in the retina of Bufo marinus.

The number, cell morphology and retinal distribution of rods and cones were determined in the retina of the toad, Bufo marinus. Adult animals were sacrificed, both eyes were removed and prepared for either tangential section across the outer segments of the photoreceptor layer, or transverse section across the whole retina. Cone densities increased from an average of 7000/mm2 in the peripheral to a maximum of 25,000/mm2 in the central retina. The high cone densities extended across the naso-temporal axis of the retina corresponding to the position of the visual streak in the ganglion cell layer. The total number of cones in the retina was estimated to be 1.1 million. Rod density of 21,000/mm2 in the central retina decreased to 17,000/mm2 at 1.5-4 mm eccentricity, and then increased to 29,000/mm2 in the peripheral retina. The total number of rods amounted to about 2 million. The mean of the cross-sectional area of rod outer segments was 11.2 +/- 1.5 microns 2 (mean +/- SD) in the highest and 17.9 +/- 4.7 microns 2 in the lowest density areas of the retina. The length of the rod outer segments extended from 28 microns in the ventral peripheral retina to a maximum of 89 microns in the dorsal retina, dorsal to the visual streak of the ganglion cell layer. The results of the present study showed a differential retinal distribution of photoreceptors, with a peak density in the retinal centre and a higher density along the naso-temporal axis of the eye. We conclude that the area of high photoreceptor density, matched by high neuron densities of the INL and GCL, corresponds to the site of acute vision of the Bufo retina.

Animals↗
PubMed1985

Neuropeptide Y (NPY)-like immunoreactive amacrine cells in retinas of frog and goldfish.

The distribution of neuropeptide Y (NPY)-like immunoreactivity in rat, rabbit, chick, frog and goldfish retinas was investigated by immunohistochemistry. Positive results were observed only in the frog and goldfish retinas. NPY immunoreactivity was associated with a small population of amacrine cell bodies in the inner nuclear layer and cell processes in the inner plexiform layer of both retinas. In the frog retina, three distinct layers containing immunoreactivity were observed in the inner plexiform layer. In contrast, the immunoreactivity in the same area of the goldfish retina was more or less separated into two layers. Convincing evidence could not be found for the co-existence of NPY-like material with other putative transmitter-like substances in the two retinas. Radioimmunoassay revealed the presence of small amounts of NPY-like immunoreactivity in the rabbit retina; the goldfish and frog retinas contained significantly more immunoreactive material. High performance liquid chromatography of the immunoreactive material in frog and goldfish retinas showed each retina containing different molecular forms of NPY-like proteins, neither of which resembled porcine NPY or PYY. The endogenous NPY-like material of the frog retina can be released by potassium depolarisation in a calcium-dependent way. In view of all these data an NPY-like protein must now be considered a potential retinal transmitter.

Animals↗
PubMed1994

Is abnormal retinal development in albinism only a mammalian problem? Normality of a hypopigmented avian retina.

The central retina in hypopigmented mammals is underdeveloped. In the outer retina this deficit is confined to rods. Also, many ganglion cells in temporal regions project inappropriately to the contralateral hemisphere. This study addresses the question of whether pigment-related abnormalities occur in the central retina of a non-mammal, the bird. Birds have a highly developed central retina, but unlike most mammals they do not have a significant uncrossed retinal projection. Consequently, examination of the retinae of hypopigmented birds will reveal whether there is a relationship between the two abnormalities. Also if one of the primary effects of albinism is centred on rods, then albino birds may not show a deficit, because their retinae are cone dominated. Retinae from normally pigmented and two forms of hypopigmented budgerigars (Melopsittacus undulatus) were studied. Measurements of layer thickness, cell density and cell size were made at a range of locations in the ganglion cell layer and in the inner and the outer nuclear layers. Estimates of cone numbers were also made. Each strain of bird had an area of increased retinal layer thickness in dorso-temporal regions, but not a fovea. Although there were variations in the measurements undertaken between the strains, none were pigment related or consistent with the abnormality found in the central retina in albino mammals. Consequently, the underdevelopment of the central retina seen in hypopigmented mammals does not occur in this bird. There are two possible explanations for this result. First, normal mammalian retinal development may depend partly on time-dependent interactions in the maturation of the retinal pigment epithelium and the neural retina. Although there is a common time table for the development of the mammalian visual system when expressed in terms of the caecal period, which is between conception and eye opening, the pace of retinal development in birds is accelerated, which may alter interactions between these regions. Second, as the bird retina is cone dominated, any deficits in albino strains may be relatively minor.

Albinism↗
PubMed2004

Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina.

Mechanisms for the removal of glutamate are vital for maintaining normal function of the retina. Five excitatory amino acid transporters have been characterized to date from neuronal tissue, all of which are expressed within the retina except excitatory amino acid transporter 4 (EAAT4). In this study we examined the expression and localization of the glutamate transporter EAAT4 in the rat retina using RT-PCR and immunocytochemistry. RT-PCR using rat EAAT4 specific primers revealed a prominent 296-bp product in the retina, cortex and cerebellum. The identity of the EAAT4 fragment was confirmed by DNA sequencing. We examined the tissue expression levels of EAAT4 in cortex, retina and cerebellum using real-time PCR. The highest expression level was found in the cerebellum. Expression in the cortex was approximately 3.1% that of the cerebellum and the retina was found to have approximately 0.8% the total cerebellar EAAT4 content. In order to examine the specific cell types within the retina that express EAAT4, we performed immunocytochemistry using a rat EAAT4 specific antiserum. Cellular processes within the nerve fibre layer of the retina were intensely labelled for EAAT4. Double labelling EAAT4 with glial fibrillary acidic protein (GFAP) revealed extensive colocalization indicating that EAAT4 is localized within astrocytes within the retina. Double labelling of EAAT4 and the glutamate transporter EAAT1 (GLAST) revealed extensive colocalization suggesting that astrocytes in the retina express at least two types of glutamate transporters. These results suggest that astrocytes within the retina are well placed to provide mechanisms for glutamate removal as well as controlling cellular excitability.

Amino Acid Transport System X-AG↗
PubMed1985

Distribution of ganglion cells in the retina of adult pigmented ferret.

The retinal ganglion cell distribution in adult pigmented ferret was mapped in Nissl-stained retinas and in retinas back-filled with HRP after large bilateral injections of the enzyme into the brain. In common with other carnivores the ferret has an area of peak cell density equivalent to the area centralis and a prominent visual streak of high cell density extending horizontally across the retina. The maximum ganglion cell densities for the retinas were estimated to be 3500-5200 cells/mm2 in Nissl-stained, dehydrated retinas and 3300-4300 cells/mm2 in HRP-labelled, undehydrated retinas. Three cell types were distinguished in the HRP-labelled retinas and they appear to correspond to alpha-, beta- and gamma-cell types of cat retina. However, unlike in cat, the retinal ganglion cells of the ferret do not consistently fall into 3 distinct groups with respect to cell size, nor is there a tendency for the cells in the area centralis to be smaller than those in the peripheral retina. Estimates for the total number of ganglion cells of 82,000 and 88,000 were obtained from Nissl-stained retinas, and of 74,000, 75,000 and 78,000 from HRP-labelled retinas.

Animals↗
PubMed1992

The occurrence of three isoenzymes of protein kinase C (alpha, beta and gamma) in retinas of different species.

The localisation and immunochemical identification of 3 different forms of protein kinase C (PKC-alpha, PKC-beta and PKC-gamma) in retinas of different species were analysed by immunohistochemistry and SDS-PAGE-Western blotting, respectively. Only in some cases was there a correlation between the findings from each procedure. One reason for the lack of correlation could be the small amounts of PKC present in some retinas, which made detection possible only by first concentrating the antigen by SDS-PAGE and then carrying out Western blotting. Another possible reason is that an antibody recognises unknown antigens immunohistochemically, but, because of their specific characteristics, they are denatured when subjected to SDS-PAGE and Western blotting and therefore remain undetected. PKC-beta immunoreactivity is present in rabbit, frog and goldfish retinas but absent from the rat retina. However, SDS-PAGE and Western blotting experiments showed that the PKC-beta isoenzyme is absent from the fish retina but present in the rat retina. PKC-beta immunoreactivity in rabbit retina is present in ganglion and/or amacrine cells; in the frog retina the enzyme is associated with some bipolar cells. In the goldfish retina, PKC-beta is associated with a large population of cells in the ganglion cell layer as well as with some amacrine cell bodies. PKC-alpha is present primarily in bipolar cells of rat, fish and rabbit retinas and was not detected by immunohistochemistry or blotting experiments in the frog retina. SDS-PAGE and Western blotting of retinal extracts from different species showed that PKC-gamma occurs in the rabbit where it was associated with ganglion and/or amacrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Oxygen consumption in the rat outer and inner retina: light- and pharmacologically-induced inhibition.

Biochemical, physiological and histological data have established that 55-65% of retinal mitochondria are located in the photoreceptor inner segments and suggested that photoreceptors have at least a two-fold greater oxygen consumption (QO2) than the remaining inner retina. QO2 in isolated whole rat retina (QWR), outer retina (QOR) and inner retina (QIR) was measured during dark and rod-saturating light adaptation. The effects of function-specific chemical agents on QWR, QOR and QIR during dark and light adaptation were determined. In addition, the oxidation-reduction (redox) potential of cytochrome a3 of whole, outer and inner retina was measured during dark and light adaptation. During dark adaptation, the mean QWR was 1.62 mumol O2 (mg dry wt)-1 hr-1 and whole retinal level of reduced cytochrome a3 was 19%. They decreased by 24% and 37% during light adaptation, respectively. To determine QOR and QIR during dark and light adaptation, the outer retina was pharmacologically-isolated from inner retina using L-2-amino-4-phosphonobutyric acid plus kynurenic acid (APB/Kyn). Experiments in the presence or absence of APB/Kyn revealed that: (i) QOR, but not QIR, of the dark-adapted retina was decreased 37% during light adaptation, (ii) the outer and inner retina consumed 65% and 35% of the QWR during dark adaptation, respectively, and 54% and 46% of the QWR during light adaptation, respectively, (iii) the level of reduced retinal cytochrome a3 in the outer, but not inner, retina was decreased 34% during light adaptation, (iv) during light adaptation, the rate of QO2 was equal in the outer and inner retina, and (v) the effects of APB/Kyn were reversible. These results establish that the mean rate of QIR and retinal cytochrome a3 are unchanged during dark or light adaptation. In addition, they suggest that QOR:QIR in the rat may be modeled using a 65%:35% model during DA and a 55%:45% model during LA. All the function-specific agents--IBMX, lead, diltiazem, ouabain, CO2+ plus Mg2+ and verapamil--significantly decreased QWR during dark and light adaptation. A more detailed analysis revealed that IBMX and lead each selectively reduced (> or = 90%) QOR during dark adaptation whereas CO2+ plus Mg2+ and verapamil each selectively reduced (> or = 93%) QIR during dark and light adaptation. These results are consistent with the known pharmacological sites and mechanisms of these agents. Additional experiments determined that the IBMX- and lead-induced inhibition of QOR during dark adaptation resulted, either wholly or partially, from the influx of extracellular Ca2+. During dark adaptation in Ca(2+)-free medium: (i) QWR and QOR increased while QIR was unchanged, (ii) QOR was not decreased in the presence of IBMX and (iii) QOR was only partially decreased in the presence of lead.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1996

Clonal architecture of the mouse retina.

The study of chimeric retinas has yielded insight on the early development of retina. The close match in chimerism ratios between right and left retinas is significant and supports the idea that both retinas originate from a common population of progenitors. We are able to estimate numbers of progenitor cells that contribute to the formation of the retina and the approximate time at which this small group is isolated from surrounding prosencephalic cell fields. These cells undergo at least five rounds of division before the first retinal neurons are generated. The mouse retina is not build from the center outward. There is simultaneous expansion and differentiation in all parts of the retina and as a result clones are not arranged in wedges. Instead the mouse retina is a patchwork of clones that do not differ greatly in size from center to periphery. The most consistent radial feature in mouse retina is a raphe left at the line of fusion of the margins of the ventral fissure. Processes that shape the clonal patchwork are both passive and active, intrinsic and extrinsic. Certain features of the clonal architecture of the retina, such as the size differences of clones are primarily passive responses to extrinsic forces on progenitor cells and their progeny. The fifteen-fold range in the size of cohorts is not due to intrinsic differences in the proliferative capacity of individual progenitor cells, but is due to the extent of cell movement and mixing at early stages of development. In contrast, active or intrinsic processes are illustrated by the partial (and still controversial) restriction of retinal progenitors, the possible clonal differences between ganglion cells with crossed and uncrossed projections, and the consistent differences in ratios of albino and pigmented genotypes in peripheral and central retina.

Animals↗
PubMed1992

The development of parafoveal and mid-peripheral human retina.

The morphological development of parafoveal retina (1-1.5 mm from the foveal center) and the mid-peripheral (4 mm from the foveal center) human retina has been studied from fetal (F) 26 weeks to adulthood. At both retinal points, all layers and neuronal types are present at F26 weeks. In parafovea at F26 weeks photoreceptors have only a rudimentary inner segment and no outer segments. Short outer segments are present on both rods and cones at F36 weeks. By postnatal (P) 5-8 days the inner retina is relatively mature. Photoreceptors have elongated basal axons which cause the photoreceptor layer to become much thicker than in prenatal retina. At birth cone inner segments are untapered, but rod inner segments have already reached their adult width of 2 microns. Both rod and cone inner and outer segments are 30-50% of adult length. By 13 months both inner and outer retina are mature appearing, with the photoreceptors accounting for half the retinal thickness due to the elongation of the fibers of Henle. Cone outer segments elongate up to P5 years and rod outer segments to P13 years. At mid-peripheral or rod-ring retina outer segments are present on rods at F26 weeks and on cones at F36 weeks. At birth the inner retina is adultlike. The outer plexiform layer becomes thicker up to P45 months due to the elongation of fibers of Henle. At birth both rod and cone mid-peripheral inner segments are slightly longer and outer segments are 50% longer than in parafoveal retina. By P5 years mid-peripheral rod outer segments are slightly longer than in parafoveal retina, and this changes little thereafter. This anatomical study has found that the photoreceptors in peripheral rod-ring retina develop earlier than those in more central retina, and in turn parafoveal photoreceptors develop well in advance of foveal cones. This suggests that human neonates may utilize more peripheral retinal regions for some aspects of visual function before foveal cone vision becomes dominant.

Adolescent↗
PubMedDate not supplied

Volume transmission of dopamine may modulate light-adaptive plasticity of horizontal cell dendrites in the recovery phase following dopamine depletion in goldfish retina.

We investigated the recovery of light-adaptive spinule formation following dopamine depletion with intraocular injection of 6-hydroxydopamine (6-OHDA) and subsequent neogeneration of dopamine interplexiform cells (DA-IPC) at the marginal zone. DA-IPCs were gone by 2 weeks postinjection and appeared at the marginal zone by 6 weeks postinjection, at which time DA-IPC neurites grew toward the central retina, reaching within 0.5 mm of the central retina by 1 year. Retinas from day time, light-adapted fish at 2 weeks, 4 weeks, 3 months, and 1 year postinjection with 6-OHDA were processed for pre-embedding tyrosine hydroxylase immunoreactivity (TOH-IR) and compared to sham-injected and control retinas at the electron-microscopical (EM) level. Only 6-OHDA fish that tilted markedly toward the injected eye were used for these experiments. The tilt mimics the dorsal light reaction, indicating a 2-2.5 log unit increase in the photopic sensitivity of the 6-OHDA eye. Spinule formation was reduced by about 60% in the 2- and 4-week 6-OHDA retinas, but returned to control levels throughout the entire retina of 3-month and 1 year 6-OHDA retinas even though the central region of these retinas contained no detectable TOH-IR. Intraocular injection with 10 microM SCH 23390 (a D1 antagonist) reduced light-adaptive spinule formation by 50% both in control eyes as well as those eyes that were 3 months post 6-OHDA injected. The full return of spinule formation with only partial reinnervation of the retina with DA-IPC processes and their subsequent inhibition by SCH 23390 indicates that dopamine diffused large distances within the retina to regulate this synaptic plasticity (i.e. displayed volume transmission). Also, since all 6-OHDA injected fish displayed an increased photopic sensitivity in the injected eye when sacrificed, we suggest that horizontal cell spinules are not required for photopic luminosity coding in the outer retina.

Adaptation, Ocular↗
PubMedDate not supplied

Tracer coupling among regenerated amacrine cells in the retina of the goldfish.

This study sought to characterize the tracer coupling of regenerated amacrine cells in the retina of the goldfish and assess the integration of regenerated neurons into existing retinal circuits. Regeneration of new neurons from injury-induced progenitors was stimulated by surgically excising a small rectangular piece of retina. Several months after regeneration was complete, intracellular injections of Neurobiotin, a gap junction-permeant tracer, were made into single regenerated amacrine cells or nonregenerated (extant) amacrine cells lying outside the regenerated patch. Two groups of amacrine cells were injected: those that in normal retina are tracer coupled and a single type (the radiate amacrine cell) that is not. The data show that regenerated amacrine cells are tracer coupled to each other and to their homologous counterparts outside the patch of regenerated retina. Regenerated radiate cells possess morphologically abnormal dendrites, but these processes can extend out of regenerated retina into surrounding normal retina. Similarly, the dendrites of extant radiate cells, severed by the original lesion, can regenerate into the patch of regenerated retina. These results indicate that in the goldfish retina the cell-specific junctional circuitry present in normal retina is re-created in the regenerated retina, and suggest that regenerated neurons are functionally integrated into the existing retina.

Animals↗
PubMed1989

The appearance and distribution of microglia in the developing retina of the rat.

We have examined the development of microglia in the rat retina, using a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Retinas were studied from animals aged from E(embryonic day)12, just after the invagination of the optic cup and prior to the closure of the optic fissure, to adulthood. The lectin also proved a sensitive label for the endothelial cells of the developing retina. Our results provide some support for the view that microglia are derived from the monocyte-macrophage series of blood cells. At E12, most labeled cells were found at the vitreal surface, suggesting that they had come from the hyaloid circulation, while some had entered the retina and appeared to be migrating towards its ventricular surface. From E14 to early postnatal ages, most labeled cells had processes and resembled the amoeboid microglial cells described in silver carbonate staining studies (Ling, 1982). The number of labeled cells rose from about 700 to E14 to a peak of about 27,000 at P(postnatal day)7, and fell to about 19,600 by P12. As early as E16, a regularity was apparent in the distribution of microglial cells over the surface of the retina, the cells tending to avoid each other. Microglial cells are found throughout the thickness of the very young retina, but as the layers of the retina differentiate, they are increasingly restricted to the inner half of the retina. Our findings indicate that microglia enter the retina well before the period of neuronal death, making it unlikely that they invade the retina solely in response to cell death. Our results confirm however that, once in the retina, microglia become associated with, and appear to phagocytose, the pyknotic debris which appears during the period of neuronal death. They also become closely associated with the retinal vasculature. In the adult, the intensity of the labeling of microglia was much reduced. Those cells which were labeled appeared more differentiated, resembling the "resting microglia" described in earlier studies.

Animals↗