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PubMed1996

[Macular combined malformation (hamartoma) of the retina and retinal pigment epithelium].

BACKGROUND: Combined malformations (hamartomas) of the retina and the retinal pigment epithelium are extremely rare. Confusion of these pigmented lesions with choroidal melanomas or other malignancies is possible. MATERIALS AND METHODS: We present the cases of a 7-year-old girl who developed accommodative convergent strabism and the case of an 8-year-old boy with deterioration of visual acuity in the left eye. On examination the anterior segments were normal in both cases. Funduscopically both eyes showed a centrally located large, partly pigmented and slightly prominent tumor, which extended fanlike into the normal-appearing retina. Both lesions were partly obscured by grayish-white, semitranslucent and thickened retina with retinal folds and overlying tortuous vessels. On follow-up examination one lesion seemed to be slightly more pigmented whereas the other lesion remained unchanged. RESULTS AND DISCUSSION: Combined malformations of the retina and the retinal pigment epithelium were originally described as clinical entities (hamartomas) by Gass in 1973. A few additional cases were subsequently published by McLean in 1976, by Laqua and Wessing in 1979 and some other authors. Laqua and Wessing were the first to give a report of a histologic study in one case with a macular lesion that showed two distinguishable components. The outer pigmented portion consisted of hypertrophied retinal pigment epithelium; the inner unpigmented portion consisted of a malformed and thickened retina which, however, showed normal layering. The clinical characteristics are usually diagnostic. Fluorescein angiography is helpful in establishing the diagnosis and ruling out differential diagnoses. CONCLUSION: Although long-term follow-up did not show evidence of growth patients with combined malformation of the retina and retinal pigment epithelium should be followed up regularly.

Child↗
PubMed2004

Temporal shifts in visual pigment absorbance in the retina of Pacific salmon.

The visual pigments and photoreceptor types in the retinas of three species of Pacific salmon (coho, chum, and chinook) were examined using microspectrophotometry and histological sections for light microscopy. All three species had four cone visual pigments with maximum absorbance in the UV (lambda(max): 357-382 nm), blue (lambda(max): 431-446 nm), green (lambda(max): 490-553 nm) and red (lambda(max): 548-607 nm) parts of the spectrum, and a rod visual pigment with lambda(max): 504-531 nm. The youngest fish (yolk-sac alevins) did not have blue visual pigment, but only UV pigment in the single cones. Older juveniles (smolts) had predominantly single cones with blue visual pigment. Coho and chinook smolts (>1 year old) switched from a vitamin A1- to a vitamin A2-dominated retina during the spring, while the retina of chum smolts and that of the younger alevin-to-parr coho did not. Adult spawners caught during the Fall had vitamin A2-dominated retinas. The central retina of all species had three types of double cones (large, medium and small). The small double cones were situated toward the ventral retina and had lower red visual pigment lambda(max) than that of medium and large double cones, which were found more dorsally. Temperature affected visual pigment lambda(max) during smoltification.

Aging↗
PubMed2005

Lamina formation in the Mongolian gerbil retina (Meriones unguiculatus).

Retinae of nocturnal rodents, such as mice and rats, are almost exclusively rod-dominated. The gerbil, in contrast, shows active periods during day and night and uses both rod- and cone-based vision. However, its retina has not been studied in detail, except for one developmental study analysing its prenatal period (Wikler et al. 1989). Here, the formation of the laminar structure of the gerbil retina was studied from birth until late adult stages. At birth, the retina consisted of a wide neuroblastic layer, with 30% of cells still dividing, a rate decreasing to nearly zero by P6. Shortly after birth, segregation of a ganglion cell layer began. All retinal layers reached their final size around P20, as determined from DAPI-stained cryosections. Muller glial cells developed their typical structure from P1 onwards, e.g. announcing an outer plexiform layer (OPL) at P5, as analysed by the Ret-G7 and glutamine synthetase antibodies. The analyses of the inner retina were performed by antibodies to calretinin (CR) and calbindin (CB). CR is expressed in ganglion cells followed by amacrine cells from P1 onwards; their processes formed four subbands in the inner plexiform layer (IPL) and appeared sequentially after P5 until P20. CB stained a subtype of horizontal cells with their processes into the OPL from P14 onwards. The rod-specific antibody rho4D2 announced photoreceptors at P4, showing signs of outer segments from P10 onwards. The study shows that the formation of all retinal layers in the gerbil occurs postnatally. This and the fact that the gerbil retina is not exclusively rod-dominated could render the gerbil a valuable model for in vitro studies of retinogenesis in rodents.

Aging↗
PubMed1997

Early expression of recoverin in a unique population of neurons in the human retina.

The calcium-binding protein recoverin has been reported as present in photoreceptors, cone bipolar cells and sparse cells in the ganglion cell layer in the adult retinae of various vertebrate species. The present study was undertaken to clarify the developmental pattern of recoverin-immunoreactive cells in the human retina with particular attention to the cells in the inner retinal layers. In the adult human retina, small populations of recoverin-containing cells are present in the ganglion cell and nerve fiber layers. However, the precursors of these cells are quite numerous on the inner and outer borders of the nerve fiber layer in the fetal retina. By 13 weeks of gestation these cells express recoverin very intensely. By 24 weeks they are mature-looking with relatively large soma sizes (mean = 118 microns 2) and appear round, oval or multipolar in shape, with varying numbers of short processes. There follows a noticeable reduction of the mean soma size, but little change in morphology and process number during the remaining gestational stages up to and after birth. The mean numerical density of the recoverin-positive cells in the fetal inner retinal layers is gradually reduced from the high level at 13 weeks until birth, when there is a great drop to the adult level. The recoverin-immunoreactive cells in the ganglion cell layer demonstrate distinctively different developmental and morphological features from the principle neurons and glial cells in the retina. They are probably the neurons derived from the marginal zone of the retinal primordium that reside in the inner and outer borders of the nerve fiber layer due to the invasion of ganglion cell axons. The expression of recoverin in the neurons may be significant in maintaining an inside-out and centroperipheral gradient of calcium concentration in the premature retina, thereby playing a role in determining the polarity of the differentiating ganglion cells and the growth of their axons in a centrifugal spatiotemporal order.

Antibody Specificity↗
PubMed2003

Reduced programmed cell death in the retina and defects in lens and cornea of Tgfbeta2(-/-) Tgfbeta3(-/-) double-deficient mice.

We have previously shown that immunoneutralization of transforming growth factor-beta (TGF-beta) in the chick embryo significantly reduces programmed cell death (PCD) in peripheral neurons, spinal cord, and retina. In order to validate these results we have begun to analyze PCD in mice with targeted ablations of the TGF-beta2 and TGF-beta3 genes. Recent analyses of mice lacking TGF-beta3 had failed to reveal an overt eye phenotype, while retinae of TGF-beta2-deficient mice showed retinal hypercellularity. We report now that eyes of Tgfbeta2/Tgfbeta3 double-deficient mice display severe alterations in the morphology of the retina, lens, and cornea. The inner neural retina-the region where TGF-beta receptor (TbetaR) I and II immunoreactivities are most prominent-is significantly thickened, and numbers of TUNEL-positive cells are significantly reduced compared to wild-type littermates. In Tgfbeta2(-/-) Tgfbeta3(-/-) and Tgfbeta2(-/-) Tgfbeta3(+/-) littermates the retina was consistently detached from the underlying pigment epithelium. Cornea, corneal stroma, and lens epithelium were significantly thinner in these mutants. In contrast, retinal morphology in Tgfbeta2(+/-) Tgfbeta3(-/-)mutant littermates resembles the situation observed in wild-type retinae except for the retinal detachment. Thus, regression in the thickness of cornea and corneal stroma seems to be TGF-beta isoform and gene dose dependent. Our results substantiate the notion based on previous analyses of chick embryos with reduced levels of endogenous TGF-beta that TGF-beta, most notably TGF-beta2, is required to mediate PCD in developing retinal cells in vivo. Moreover, our data indicate that TGF-betas play essential roles in cornea and lens development.

Activin Receptors, Type I↗
PubMed1996

The spatio-temporal pattern of photoreceptor degeneration in the aged rd/rd mouse retina.

Photoreceptor degeneration in the retina of the rd/rd (retinal degeneration) mice has been studied using immunocytochemistry with antisera against cone- and rod-opsin. The rd/rd mice exhibited different regional specific rates of degeneration for rods and cones. As early as postnatal day 25, cells labelled with the rod-opsin and cone-opsin antisera disappeared preferently from the central retina. Whereas in the inferior half of the retina, degeneration subsequently proceeded towards the periphery, this did not occur in the dorsal hemisphere. By the age of 100 days, many cells immunoreactive for the cone-opsin antiserum and a few cells immunoreactive for the rod-opsin antiserum were located in an area of the dorsal retina. The ventral retina lacked labelled elements at this age. Finally, rd/rd mice at one year or 600 days of age contained a similar number of cone-opsin immunopositive cells (approximately 2000-2800 cells), occupying almost the same area in the retina as that found at 100 days of age. A photoreceptor candidate for the entrainment of non-visual photoreception probably remains in the cone population in aged rd/rd mice.

Aging↗
PubMed1997

Comparative investigations of the neuronal apparatus in the pineal organ and retina of the rainbow trout: immunocytochemical demonstration of neurofilament 200-kDa and neuropeptide Y, and tracing with DiI.

The retina and pineal organ of the rainbow trout have been investigated immunocytochemically with antibodies against neurofilament 200-kDa (NF-200) and neuropeptide Y (NPY), which are known to label horizontal and amacrine cells in the retina of several vertebrates. The NF-200 immunoreaction stains horizontal cells of the retina, but not neuronal perikarya in the pineal organ. Axons of both the optic and the pineal tract display immunoreaction for NF. The NPY immunoreaction labels a population of amacrine cells in the retina, but is not detected in neuronal perikarya of the pineal organ. Single NPY-immunoreactive nerve fibers have been located in the capsule of the pineal organ. The data suggest that neurons corresponding to NF-200-immunoreactive horizontal and NPY-immunoreactive amacrine cells of the retina are missing from the pineal organ of the trout. Thus, the neuronal apparatus in the light-sensitive pineal organ appears to be less complex than that in the retina. This has been confirmed by tracing experiments with DiI: intrapineal neurons retrogradely labeled via the pineal tract are found in a postsynaptic location to processes of photoreceptor cells containing synaptic ribbons. These results indicate a bineuronal chain in the pineal organ of the rainbow trout comprising the photoreceptor cell as the first neuron and the ganglion cells forming the pineal tract as the second neuron. The NPY-immunoreactive nerve fibers in the capsule of the pineal organ may represent an autonomic innervation.

Animals↗
PubMed1998

Calcium-binding proteins in the retina of a calbindin-null mutant mouse.

Calcium-binding proteins are abundantly expressed in many neurons of mammalian retinae. Their physiological roles are, however, largely unknown. This is particularly true for calcium-modulating proteins ("calcium buffers") such as calbindin D28k. Here, we have studied retinae of wildtype (+/+) and calbindin-null mutant (-/-) mice by using immunocytochemical methods. Although calbindin immunoreactivity was completely absent in the calbindin (-/-) retinae, those cells that express the protein in wildtype retinae, such as horizontal cells, were still present and appeared normal. This was verified by immunostaining horizontal cells for various neurofilament proteins. In order to assess whether other calcium-binding proteins are upregulated in the mutant mouse and may thus compensate for the loss of calbindin, mouse retinae were also immunolabeled for parvalbumin, calretinin, and a calmodulin-like protein (CALP). In no instance could a change in the expression pattern of these proteins be detected by immunocytochemical methods. Thus, our results show that calbindin is not required for the maintenance of the light-microscopic structure of the differentiated retina and suggest roles for this protein in retinal function.

Animals↗
PubMed1999

The cytoskeleton-associated neuronal calcium-binding protein caldendrin is expressed in a subset of amacrine, bipolar and ganglion cells of the rat retina.

Caldendrin is a novel calcium-binding protein confined to the somatodendritic compartment of neurons. Here we have studied the expression pattern of caldendrin in the rat retina. First we assessed the distribution of caldendrin transcripts in the adult and developing retina by in situ hybridization. In the adult retina, transcripts are expressed mainly in the inner half of the inner nuclear layer (INL) and to a lesser extent in the ganglion cell layer (GCL). During development labeling of the inner part of the cytoblast layer, where amacrine cells reside, is already present at postnatal day 1 (P1). The intensity of hybridization signal in this sublamina of the developing INL increases up to P8, whereas significant labeling in the GCL was first found at P14, coinciding with eye opening. Immunodetection with a polyclonal antibody revealed intensive staining of cells in the inner retina, which are presumably mainly amacrine and significantly fewer bipolar and ganglion cells. All parvalbumin-containing All amacrines were immunopositive for caldendrin. Colocalization with calbindin was found in cone bipolar cells, the majority of AII amacrines, and calbindin-positive cells in the GCL. In the GCL, caldendrin was also colocalized with calretinin-immunopositive cells. Most caldendrin-positive amacrine cells in the adult rat retina were glycinergic and only a few were GABAergic. In retinal flat mounts, it was confirmed that less than 10% of retrogradely labeled retinal ganglion cells (RGC) are caldendrin-positive. Caldendrin immunoreactivity does not colocalize with tyrosine hydroxylase, VIP, substance P and somatostatin immunoreactivity. In summary, caldendrin expression is regulated differentially in retinal cell types during development and is restricted to a subpopulation of amacrine, bipolar, and ganglion cells, suggesting specific functions in the developing and mature retina.

Animals↗
PubMed2000

Cholesterol synthesis in the vertebrate retina: effects of U18666A on rat retinal structure, photoreceptor membrane assembly, and sterol metabolism and composition.

Treatment of neonatal rats with U18666A, an inhibitor of desmosterol delta24-reductase, results in accumulation of desmosterol (delta5,24) and depletion of cholesterol (delta5) in various bodily tissues and also causes cataracts. We evaluated the effects of U18666A on the sterol composition, de novo sterol synthesis, and histological structure of the retina. Neonatal Sprague-Dawley rats were injected subcutaneously with U18666A (15 mg/kg, in olive oil ) every other day from birth through 3 wk of age; in parallel, control rats received olive oil alone. At 21 d, treated and control groups each were subdivided into two groups: one group of each was injected intravitreally with [3H]acetate; retinas were removed 20 h later and nonsaponifiable lipids (NSL) were analyzed by radio-high-performance liquid chromatography. The other group was injected intravitreally with [3H]leucine; 4 d later, one eye of each animal was evaluated by light and electron microscopy and light microscopic autoradiography, while contralateral retinas and rod outer segment (ROS) membranes prepared therefrom were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. In the treated group, the delta5/delta5,24 mole ratio of retinas was ca. 1.0, and >88% of the NSL radioactivity was in delta5,24; in contrast, control retinas had delta5/delta5,24 >170, with >80% of the NSL radioactivity in delta5. Retinal histology, ultrastructure, ROS renewal rates, and rhodopsin synthesis and intracellular trafficking were comparable in both treated and control animals. These results suggest that desmosterol can either substitute functionally for cholesterol in the retina or it can complement subthreshold levels of cholesterol by sterol synergism.

Acetates↗
PubMed1976

Ether lipid content of phosphoglycerides from the retina and brain of chicken and calf.

Phospholipid contents and compositions were determined for chicken and calf retinas, chicken brain and calf gray matter. Retinal phospholipid compositions differ from brain phospholipid compositions by including a higher percentage of choline phosphoglycerides and lower percentages of ethanolamine and serine phosphoglycerides. The proportion of sphingomyelin is lower in calf retina than in calf brain. Among the ethanolamine phosphoglycerides, the proportions of the alk-1-enylacyl (plasmalogen) type are lower and the proportions of alkylacyl and diacyl types are higher in retina than in brain. The alkyacyl glycerophosphoethanolamines accounted for 7.6% and 8.9% of the ethanolamine phosphoglycerides from chicken and calf retinas respectively. Lower proportions of plasmalogens in the choline phosphoglycerides were found in retina as compared with brain. The alkylacyl glycerylphosphocholines comprised 4.0% of the retinal choline phosphoglycerides. Overall, a smaller proportion of retinal phosphilipids than of brain phospholipids contained alkyl or alk-1-enyl ether groups and the ratio of alkyl groups to alk-1-enyl groups was greater in retina than in brain.

Animals↗
PubMed1988

Histamine H1-receptor in the retina: species differences.

Histamine H1-receptors in membranes of the various mammalian retinas were studied by [3H]mepyramine binding assay. Specific [3H]mepyramine bindings to bovine, pig, dog and human retinas were observed with the dissociation constants (KD), 3.8 +/- 1.2 nM, 1.8 +/- 0.6 nM, 2.6 +/- 0.6 nM and 3.0 +/- 0.9 nM, respectively, which were similar to those found in brains. But there was no detectable specific binding in the guinea-pig and rabbit retinas. The number of binding sites (Bmax) ranged from negligible value to 290.7 +/- 51.7 fmole/mg protein(human retina). Some H1-antagonists acted as potent agents in competing with [3H]mepyramine binding to bovine and pig retinas. These results indicated that histamine H1-receptors exist in some mammalian retina and have similar characteristics to those in brain membranes, but they distributes in the wide difference of the binding capacities among the species, while in brain variations were smaller.

Animals↗
PubMed1976

Light-evoked release of glycine from cat and rabbit retina.

The light-evoked release of [3H]glycine from retina in cat (in vivo) after pre-retinal perfusion and in rabbit (in vitro) after intravitreal injection was studied. The site of uptake of [3H]glycine into retina was checked by autoradiography and was found to be almost exclusively in a type of amacrine cells. If the retina loaded with [3H]glycine was stimulated by light flashes the release increased significantly in both in vivo and in vitro experiments. When the flashing light was exchanged for continuous light there was not change in the spontaneous efflux of radioactivity. Chromatographic experiments showed that the main part of the radioactivity released by light was glycine. The light-evoked release of glycine from retina was dependent on temperature and Ca2+. Low temperature (+2 to +4 degrees C) abolished the increased release. If Ca2+ was ommitted from the perfusion medium and EDTA was added there was no light-inducable change in the efflux of radioactivity in retinas loaded with [3H]valine. The present results, that light stimulation will release glycine from the retina both in vivo and in vitro, are further criterion for it as neurotransmitter.

Animals↗
PubMed1977

Monoamine oxidase in developing chick retina.

The developmental changes in monoamine oxidase (MAO) activities towards 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) in chick retina were investigated. The whole pattern of the developmental changes in MAO activity towards 5-HT was similar to that towards PEA, even though the activity towards 5-HT was much lower than that towards PEA during the period from the 12th day of incubation to the 14th day after hatching. The MAO activities on the 12th day of incubation were low and increased remarkably until the 18th day of incubation. Then they remained unchanged until the 7th day after hatching; therefore, they decreased. The activities measured on the 14th day after hatching are on the same level as those of an adult. The multiplicity of MAO in the retinae of a chick on the 12th day of incubation and of an adult was also studied with specific inhibitors. The result showed that the major part of MAO in chick retina is type B enzyme; that type A MAO in the retina of an adult is, however, relatively higher than that in the retina of the embryo on the 12th day of incubation. It was found that an appreciable amount of MAO activity towards 5-HT in chick retina is due to type B MAO.

Age Factors↗
PubMed1981

Specific [3H]strychnine binding associated with glycine receptors in bovine retina.

Saturable, specific [3H]strychnine binding can be demonstrated in homogenates of bovine retina. Scatchard plots revealed only one set of binding sites with a dissociation constant (Kd) of about 60 nM and a maximal number of binding sites of about 1.5 pmol/mg protein. The structural specificity of [3H]strychnine binding sites in bovine retina parallels the properties found for [3H]strychnine binding sites in the spinal cord of several vertebrates. Thus, the data do not give any evidence that specific [3H]strychnine binding in bovine retina labels taurine rather than glycine receptors and favors glycine rather than taurine as inhibitory neurotransmitter in bovine retina. The subcellular distribution of specific [3H]strychnine binding in bovine retina parallels that of sodium-dependent, high-affinity uptake of glycine and taurine. All 3 parameters are mainly found in the P2 fractions of bovine retina homogenates, containing conventional synaptosomes, most abundant in the inner plexiform layer, but can also be found in the P1 fractions, containing large synaptosomes from the photoreceptor cell layer.

Animals↗
PubMed1984

Substance P in the chick retina: effects of light and dark.

Monoclonal antibodies against substance P were used to study the distribution of the peptide in the retinae of chicks that had been kept in either total darkness or brightly lit conditions. In retinae from light-adapted chicks, substance P was found to be in normal sized amacrine cells and giant cells in the inner nuclear layer, in fibres in sublaminae 1,3-5 in the inner plexiform layer, in cells in the ganglion cell layer which may have been mostly displaced amacrine cells and in a few fibres in the optic nerve fibre layer. There was no apparent concentration of immunoreactive cell bodies in any part of the retina. After dark-adaption of the birds, the immunoreactivity in the retinae was much reduced; there were fewer visible cells in all parts of the retina and there was no reaction in the inner plexiform layer. When birds were taken from the dark and kept in the light for different periods, there was a gradual increase in the number of cells and in the overall immunoreaction. Substance P is thus like several other putative retinal neurotransmitters in that its concentration in the retina is regulated by light/dark. These experiments do not indicate how the changes occur, but they underline the need for a strict control of lighting conditions in experiments with these relatively slowly metabolized neurotransmitters.

Animals↗
PubMed1985

Neuronal damage in the rat retina after chronic stress.

Long-term exposure to escapable foot shock has been used to determine if chronic stress influences neuronal cell death in the retina of albino and pigmented rats. Histopathologic and morphometric approaches analyzed changes in photoreceptors and neurons of the bipolar and ganglion cell layers of the retina. Albino Fischer rats when exposed to chronic stress for 4-8 h daily for 1 week to 6 months, developed severe retinal damage, as compared to unstressed control retinas, with reduction in photoreceptor and bipolar neurons, particularly in the superior central retina. The damage was observed in male and female rats, but males appeared to be more susceptible to the influence of stress than female animals. Ganglion cells were unaffected. Photoreceptor destruction did not occur in Long-Evans pigmented rats under identical experimental conditions. The results suggest that: input of the sensory stimulus, light, to the retina of stressed rats augmented neuronal damage and might be required for its initiation; and hormones and/or neurotransmitters associated with long-term chronic stress might be related to increased neuronal cell death in the mammalian retina.

Albinism↗
PubMed1985

So-called interplexiform cells immunoreactive to tyrosine hydroxylase or somatostatin in rat retina.

The morphology of so-called interplexiform (IP) cells immunoreactive to tyrosine hydroxylase (TH) or somatostatin (SOM) in the rat retina was described in comparison with those in the carp retina. In frozen cross-sections of the rat retina, many processes of TH-like immunoreactive cells were found to extend toward the outer plexiform layer (OPL), forming a thin layer of network fibers. A few of them further extended into the photoreceptor cell layer; such fibers were never found in the carp retina. Some processes of SOM-like immunoreactive cells in the rat retina were found to travel across the inner nuclear layer and appeared to poorly develop a network at the OPL. In the carp retina, on the other hand, only one exceptional cross-section contained such an ascending process.

Animals↗