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Immune cells in the porcine retina: distribution, characterization and morphological features.

PURPOSE: To investigate the presence of immunocompetent cells in the porcine retina and to compare the findings with those obtained earlier in human retinas. METHODS: Retinal wholemounts or cryostat sections from outbred Dutch Landrace pigs were analyzed for the presence of microglia (CD45), macrophages-monocytes (SW3, CD163, 2A10, CD14), major histocompatibility complex (MHC) class II-positive cells (MCA1335), granulocytes (MCA1219), B lymphocytes (IgM), and T lymphocytes (CD6, CD4, CD8), by using specific monoclonal antibodies followed by immunohistochemical staining. RESULTS: A uniform distribution of CD45-positive microglial cells was observed throughout the porcine retina (mean number, 289 +/- 16 cells/mm(2)). The microglia were observed along blood vessels and within the tissue between the inner limiting membrane and the inner nuclear layer. MHC class II-positive cells were mainly observed along the large- and middle-sized retinal blood vessels. Double-staining experiments showed that 54% of the microglial cells lining the larger retinal vessels were MHC class II positive. Macrophages were only incidentally observed along the larger retinal blood vessels. No T lymphocytes, B lymphocytes, monocytes, or granulocytes were observed within the retinal tissue. CONCLUSIONS: The porcine retina contains a rich network of microglial cells. Approximately half of the microglial cells lining the larger retinal vessels express MHC class II. The normal porcine retina is devoid of lymphocytes, monocytes, and granulocytes. The distribution of immunocompetent cells in the porcine retina largely resembles that observed in the human retina.

Animals↗

Pre- and Postsynaptic Sites of Action of mGluR8a in the mammalian retina.

PURPOSE: The distribution of the most recently identified metabotropic glutamate receptor type 8a (mGluR8a) in the mammalian retina is unknown, but it is known to function as a presynaptic autoreceptor in rod photoreceptors. In this study, the localization of mGluR8a in the adult rat, mouse, and rabbit retina and during postnatal development of the rat retina was analyzed. METHODS: mGluR8a immunoreactivity was detected using immunocytochemistry and light and electron microscopy. RESULTS: mGluR8a expression was found in both synaptic layers and in extrasynaptic locations, predominantly on the somata of ganglion, amacrine, and horizontal cells. This distribution pattern is different from the localization patterns of the other members of group III mGluRs in the mammalian retina, which are restricted to either the outer plexiform layer (OPL) or the inner plexiform layer (IPL). Analysis of the expression of mGluR8a at the ultrastructural level in rat retina showed that the receptor is localized pre- and postsynaptically in the OPL and postsynaptically in the IPL. During postnatal development, mGluR8a was expressed at synapses in parallel with synapse formation, but appeared earlier at extrasynaptic sites. CONCLUSIONS: These results suggest that mGluR8a is involved in synaptic processing in both plexiform layers and in both the scotopic and photopic pathways in the mammalian retina. The authors propose that, depending on its localization-pre- versus postsynaptic-mGluR8a modulates the release of L-glutamate by photoreceptors and the responses of retinal neurons to inhibitory and excitatory neurotransmitters, respectively. Furthermore, mGluR8a may have regulatory functions during neuronal development of the mammalian retina.

Animals↗

Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina.

PURPOSE: To measure the concentrations of polyamines, determine their cellular and subcellular localization, and analyze effects of their depletion in developing rabbit retina. METHODS: Isolated retinas at different developmental stages were analyzed for polyamine content by high-performance liquid chromatography (HPLC). An antibody against polyamines was used to localize endogenous stores in both freshly harvested retinas and neonatal retinal explants. To determine the effects of polyamine depletion on immature retina, neonatal explants were cultured in the presence or absence of alpha-difluoromethylornithine (DFMO), an inhibitor of the polyamine synthetic enzyme ornithine decarboxylase (ODC). Similar studies were also performed on dissociated cell cultures. Tissue was assessed using standard histologic stains as well as cell-specific markers (peanut agglutinin for cone photoreceptors and calbindin for horizontal cells). RESULTS: Retinal polyamine content was highest at birth, remained relatively high during the first postnatal week, and then steadily decreased to adult levels. At all ages analyzed, spermine concentration was higher than putrescine or spermidine; however, the differential was greatest in the adult. Polyamine immunoreactivity was localized to distal processes of both rods and cones during development. Strong immunoreactivity was maintained in adult cone inner and outer segments; comparatively weak staining was observed in the adult rods. Heavy staining of ganglion cells was present throughout development but was localized in the cytoplasm in immature cells and in the nucleus in the adult. Amacrine cells stained only in the adult. Polyamine depletion caused a disruption of immature cones, evident in the loss of their somata in the outer nuclear layer, in their processes in the outer plexiform layer in retinal explants, and in their decreased association with horizontal cells in dissociated cell culture. CONCLUSIONS: The relatively high concentrations of polyamines in neonatal retina and their discrete localization in developing photoreceptor outer segments and ganglion cells suggests an important role for these compounds in development. The disruption of cone-specific markers in polyamine-depleted retinas indicates a specific reliance on polyamines for expression of normal cone morphology or morphologic development. These developmental effects may involve polyamine-sensitive ion channels, which are known to exist in retina, or direct interactions with specialized cytoskeletal elements within outer segments.

Aging↗

Gene discovery in the embryonic chick retina.

PURPOSE: The chick embryo is a powerful model system for the study of retinal development. However, analysis of gene expression in the chick retina has lagged behind biological studies. The purpose of this study was to identity and characterize genes expressed in the chick embryo retina as candidate molecules involved in the development and function of photoreceptors and other retinal cell types. METHODS: RNA from embryonic day (ED) 18 White Leghorn chick embryo retinae was used to generate an oligo dT-primed cDNA library. Bacterial colonies representing five thousand individual clones were arrayed onto nylon membranes using a microarray robot. Replicate membranes were hybridized with cDNA probes synthesized from ED 18 retina, brain and liver. Clones that appeared preferentially expressed in retina were identified by homology searches, and their spatial and temporal expression patterns were analyzed by in situ hybridization. RESULTS: Two hundred and seventy-two clones were identified. Approximately forty percent of the clones represented potential novel genes, including ESTs, hypothetical proteins and clones with no assigned identities. Furthermore, many genes were identified that are the putative chick orthologues of genes cloned from other species. We determined the expression pattern of several clones for which sequence homologies suggested possible roles in transcriptional regulation, apoptosis or intercellular signaling. Their corresponding mRNAs were expressed in the embryonic retina in topographically specific, developmentally regulated patterns. CONCLUSIONS: We identified and characterized genes in the chick embryo retina using a combination of microarray analysis and in situ hybridization. Analysis of the expression patterns suggests involvement of several of these genes in key events during embryogenesis.

Animals↗

Growth of the postnatal rat retina in vitro: quantitative RT-PCR analyses of mRNA expression for photoreceptor proteins.

PURPOSE: To investigate whether previously reported changes in protein expression of middle and long (M/L) and short (S) wavelength cone opsin pigments in cultured retina are correlated with changes in their gene expression. Additionally, to elucidate the importance of a functional retinal pigment epithelium for the development of photoreceptor outer segments. METHODS: Neonatal rat retinas were maintained in culture for 11 days and either fixed in 4% paraformaldehyde for immunohistochemistry or prepared for RNA extraction, reverse transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR. S-cone and M/L-cone photoreceptors as well as rod photoreceptors were immunohistochemically identified using specific antibodies. Peanut agglutinin (PNA)-lectin histochemistry was used to identify interphotoreceptor matrix associated with cone photoreceptors. Immunolabeling for ED-1 and RPE65 was performed in combination with PNA-lectin staining to examine interactions between photoreceptor cells and the retinal pigment epithelium. Relative estimates of mRNA expression levels for M/L-opsin, S-opsin, recoverin, and rhodopsin in normal and cultured retina were determined by using quantitative RT-PCR. RESULTS: Strong immunolabeling for recoverin and rhodopsin accumulated in outer segments as well as photoreceptor somata in vitro. Cultured and normal retinas showed similar relative expression levels of recoverin and rhodopsin mRNA. In cultured rat retina, the density of S-cones was high and M/L-cones could not be immunohistochemically detected. However, M/L-cone photoreceptor mRNA was detectable, but at a fourfold lower level in cultured than in vivo retinas. The S-cone photoreceptor mRNA level was almost twofold lower than in vivo. Retinal pigment epithelium cells in cultured specimens showed no RPE65 immunolabeling, but expressed immunolabeling for ED-1 indicating phagocytic activity of these cells in vitro. CONCLUSIONS: We assume that the high density of S-cones and virtually no M/L-cones seen in in vitro retinas might represent an immature stage with numerous S-cones and suppressed transdifferentiation into M/L-cone phenotype. A non-functional relationship between photoreceptor cells and a dysfunctional retinal pigment epithelium may have severe consequences for the development of outer segments.

Animals↗

Natriuretic peptide system in the human retina.

PURPOSE: The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Natriuretic peptides are known to inhibit vascular cell growth and regulate vessel tone. There is also much evidence to suggest they modulate vascular permeability and angiogenesis, as well as regulating aqueous humor production in the eye. All these data indicate that the natriuretic peptide system might be involved in the development of diabetic retinopathy and glaucoma. Given the expression pattern of natriuretic peptides (NPs) and their receptors, natriuretic peptide receptor A (NPRA), natriuretic peptide receptor B (NPRB) and natriuretic peptide receptor C (NPRC) in the human retina has not yet been established, the present study was designed to determine ANP, BNP and CNP gene expression and localize the mature peptides in this tissue. The expression pattern of the genes encoding the different NP receptor subtypes was also examined. METHODS: Eyes (n=10) from human donors with no history of eye disease were fixed and processed for routine paraffin embedding. The cellular location of the NPs was established by immunohistochemistry. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of NP and NP receptor genes in neural retinas obtained from the contralateral eyes. RESULTS: Immunohistochemistry revealed the presence of NPs in the neural retina and retinal pigment epithelium. Positive NP immunostaining was observed within the astrocytes and in their processes enveloping vessels. In the anterior portion of the optic nerve, NPs were intensely labeled in neural bundles. We were able to detect NP gene expression in the human retina. The levels of NP receptor-encoding transcripts detected indicated no significant differential expression of genes coding for the different receptor subtypes. CONCLUSIONS: Our finding that NP receptor transcripts are expressed along with ANP, BNP, and CNP mRNA in the human retina provides evidence for a local system in this tissue. The expression of NPs in neural retinal, glial, and vascular elements of the normal adult retina suggests a role for these peptides in maintaining both the neural and vascular integrity of the mature retina.

Adolescent↗

[Oxidative damage and photoreceptor cell apoptosis in contusion injury of the rabbit retina].

OBJECTIVE: To study the mechanism of retina injury and photoreceptor apoptosis after contusion as well as their triggering factor. METHODS: The rabbit retina was injured by a 3 J energy contusion caused by a free falling iron bar hitting the cornea. The morphologic changes of the retina were observed by light and electron microscopes. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique was used to assess apoptosis. The amount of the malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the retina were assayed and analyzed statistically. RESULTS: Apoptosis of photoreceptors was present in retina contusion caused by a 3 J energy injury. After contusion, the MDA level increased gradually. The activity of SOD increased reflectively at first, then decreased markedly 3 days after the contusion, which was parallel with the appearance of apoptotic photoreceptors. CONCLUSIONS: Apoptosis is an important mechanism of retina contusion. Free oxygen radicals are the important triggering factors for the apoptosis of photoreceptors in the retina contusion of the rabbits.

Animals↗

[Flourescein angiography and ultrastructure studies on retina after laser photocoagulation].

OBJECTIVE: The fluorescein angiographs and ultrastructure changes as well as the repairable process of retina after photocoagulation were analyzed to provide scientific basis for the rationale of using laser in the treatment of retinal lesions. METHODS: Normal retinae were coagulated using I, II, III grade photic spots and were exposed to fluorescein angiography 1, 3, 7 days before the necessary exenteration in conformity with the informed consent given by 7 patients with malignant tumor of orbit. The retina from the removed globe was cut into thin sections and observed by use of electron microscope. RESULTS: Fluorescein angiography: Fluorescein leaked in photic spots 1 day after photocoagulation. Leakage relieved with central small fluorescein block 3 days after photocoagulation. Leakage disappeared with central fluorescein block 7 days after photocoagulation. Ultrastructure: 1 day after photocoagulation, I grade photic spot, some retinal pigment epithelium(RPE) cells were swellen and necrotic. Partial photoreceptors were lysed and disarranged. Cells of outer nuclear layer decreased in number. II grade photic spot, RPE and photoreceptors were destroyed. Some necrotic and apoptotic cells appeared in the outer nuclear layer. Structure of outer plexiform layer became disorganized. III grade photic spot, retina was destroyed severely. 3 days after photocoagulation, cell edema and debris decreased. Phagocytes appeared, RPE and Müller cells started proliferation. 7 days after photocoagulation, proliferative RPE and Müller cells replaced the damaged areas of the retina. Retinal structure disorganization increased gradually from I to III spot. CONCLUSION: Photocoagulation caused fluorescein leakage of retina, apoptosis of RPE and neuron, and damage to other structure. Subsequently, the proliferous RPE and Müller cells repaired the destroyed areas of retina.

Fluorescein Angiography↗

Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina.

PURPOSE: CNS iron accumulation is associated with several neurodegenerative diseases, including age-related macular degeneration. Intracellular overload of free iron is prevented, in part, by the iron export protein, ferroportin, and the iron storage protein, ferritin. The purpose of this study was to assess retinal localization and regulation of ferroportin and ferritin. METHODS: Normal murine retinas were analyzed by immunohistochemistry to localize ferroportin, cytosolic ferritin, and mitochondrial ferritin, with double-labeling using cell-specific markers to identify cell types. Retinas deficient in the ferroxidases, ceruloplasmin and hephaestin, accumulate iron in their retinas and RPE, while retinas deficient in iron regulatory proteins (IRPs) lack the ability to regulate several proteins involved in iron metabolism; retinas from these knockout mice along with their age matched wild type littermates were also examined to study regulation of ferritin and ferroportin. To enable visualization of label in the retinal pigment epithelial cells, sections from pigmented mice were bleached with H2O2 prior to IHC, a novel use of this technique for study of the RPE. RESULTS: In normal retinas, cytosolic ferritins were found predominantly in rod bipolar cells and photoreceptors. Ferroportin was found in RPE and Müller cells. Iron accumulation in mice deficient in ceruloplasmin and hephaestin was associated with upregulation of ferritin and ferroportin. Mice deficient in IRPs showed upregulation of ferritin and ferroportin, likely because of their inability to repress translation. CONCLUSIONS: Normal retinas contain ferritin and ferroportin, whose levels are regulated by iron-responsive, iron regulatory proteins. Ferroportin colocalizes with ceruloplasmin and hephaestin to RPE and Müller cells, supporting a potential cooperation between these ferroxidases and the iron exporter. Cytosolic ferritin accumulates in rod bipolar synaptic terminals, suggesting that ferritin may be involved in axonal iron transport. Mitochondrial ferritin increases with iron accumulation, suggesting a role in iron storage.

Animals↗

Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis).

The relationship of the vasculature to the neuronal layers was studied in whole-mounts and in sections of macaque retinas. Like other central nervous structures, primate retinas have local variations in vascularity that reflect local variations in metabolism, rather than simply tissue thickness or volume. A special feature of the retina is a dense vascular plexus in the nerve fiber layer, which is unmyelinated and hence must generate a substantial metabolic demand for ion pumping. Much of the retinal vasculature is laminated and located at specific layer boundaries. Throughout the central retina, two planes of capillaries bracket the inner nuclear layer to form a sclerad capillary network. In some regions, especially near the fovea, a second, more vitread network brackets the ganglion cell layer with another pair of capillary planes. Wherever the nerve fiber layer is thick, the vitread network becomes less planar and is multilayered. When surrounded by nerve fibers, capillaries tend to orient parallel to the fibers; when adjacent to ganglion cell bodies, the capillaries are less systematically oriented. At the border between the nerve fiber layer and the ganglion cell layer, rows of ganglion cells often interdigitate with nerve fiber bundles, resulting in local perturbations of capillary orientation. The volume of the sclerad capillary network is relatively constant at different locations, but the volume of the vitread network increases dramatically where the nerve fiber layer is thick. As a result, the vascularity of the retina is greatest in the peripapillary region near the optic disk, even though the total thickness of the peripapillary retina is comparable to the retinal thickness near the foveal crest. As many as 60-70% of the photons passing through the retina in the peripapillary region will encounter one or more capillaries before reaching a photoreceptor. Median capillary diameter increases with retinal depth from 4.5-4.7 microns in the nerve fiber layer to 5.0 microns at the sclerad border of the inner nuclear layer. Capillary diameter in the nerve fiber layer also increases near the optic disk.

Animals↗

Retinal growth in foveated teleosts: nasotemporal asymmetry keeps the fovea in temporal retina.

Fish retinas continue to grow throughout life by adding neurons at the margin, with the result that cells born at a peripheral site are steadily displaced toward the center of the enlarging retina. This presents a functional problem for fish with specialized temporal areas such as a fovea--how to reconcile continual growth with the maintenance of a temporal location for the fovea. One possibility is that the retina grows asymmetrically, with most new retina added nasally, relatively little temporally. I have tested this hypothesis by evaluating retinal growth in marine teleosts from 15 families, both foveated and unfoveated. The pattern of growth was revealed by exploiting the fact that each new generation of ganglion cells sends its axons into the optic nerve as a cohort; small grains of the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine were applied to various sites in the cross section of the optic nerves of adults, and the retrogradely labeled cell bodies in the retina were visualized in whole-mounts. The labeled cells lay in annuli, each one a generation of ganglion cells. Representatives of seven of the families showed clearly asymmetric growth: the labeled annuli were close together on the temporal side and more distant nasally, the embryonic fissure curved from its ventral origin toward the temporal side, and in six of these families, labeled fibers from temporal retina skirted the fovea. Members of the other eight families, without specialized areas, had more symmetric retinal growth: labeled annuli were equally spaced on all sides, the embryonic fissure was vertical, and there were no skirting fibers. The following hypothesis is supported: the retina grows asymmetrically, and maintains the area for acute vision oriented toward the anterior field.

Animals↗

Gene expression changes in the retina following optic nerve transection.

PURPOSE: To obtain and analyze the gene expression profiles of the retina following optic nerve transection (ONT). METHODS: An axotomy animal model was generated by taking a cross section of the optic nerve with care not to damage the adjacent blood supply. The extent of cell loss was evaluated by counting cells in the ganglion cell layer (GCL) of flat-mounted retinas stained with cresyl violet. Gene expression profiles of control and ONT retinas were analyzed with Agilent's rat oligo microarray slides. Differentially expressed genes were identified from three independent experiments and clustered based on their functions with expression analysis systematic explorer software. Real-time quantitative and semiquantitative RT-PCR were used to validate changes in gene expression levels. RESULTS: Gene expression changes in axotomized retinas were analyzed with rat oligo microarray slides containing 22,575 oligonucleotide probes that represent over 20,000 genes and expressed sequence tags (ESTs). The expression of 493 genes was increased more than 1.5 fold, including 85 that were upregulated more than 2 fold, and the expression of 113 genes was decreased 1.5 fold or more, including 21 that were downregulated more than 2 fold. Differentially expressed genes were clustered based on their functions. Several novel genes expressed in the GCL have been identified and their expression patterns in different tissues were analyzed. Among the genes differentially regulated in retinas with induced retinal ganglion cell (RGC) death, we have identified 13 genes that are mapped to known glaucoma loci and can be considered for mutation screening in patients with inherited forms of glaucoma. CONCLUSIONS: The gene expression profiles of the ONT retinas can be used to identify RGC-expressed genes, which may be essential for the morphological and physiological characteristics of RGCs. The results of this study can also be used to evaluate the molecular changes taking place in the retina in response to RGC loss.

Animals↗

[A distinct centro-peripheral gradient of development in dopaminergic amacrine cells of cat retina].

The centro-peripheral gradient of development in dopaminergic (DA) amacrine cells of cat retina has been studied by TH immunocytochemical method. Type I of TH immunoreactive neurons is typical DA cell. They reveal a clear centro-peripheral gradient of differentiation and maturation in space and time course during postnatal development. (1) At P1 stage, the TH I cells vary in TH immunoreactivity, soma sizes and dendritic maturation. Responding to degree of development, they can be divided into I1, I2 and I3. The more differentiated I1 cells, larger and darkly immuno-stained stellate cells mostly concentrates at central retina, while the less differentiated I3 cells, smaller and lightly immunostained irregular cells concentrate at peripheral retina. I2 cells of moderate differentiation distribute over all the retina. (2) During the postnatal development, from P1 to P13, the dense area of the TH I1 cells spreads peripherally in company with the increase of the total number of TH I1 cells, comprising the central 30% of the retina at P1, 65% at P6 and almost the whole of the retina by P13. After eye opening, as the TH I cells have spread at far peripheral region, the differences in soma diameters and dendritic maturation of TH I cells between central and peripheral retina decrease gradually and the centro-peripheral gradient of maturity of TH I cells becomes less distinct. At P23, no significant difference is visible in either soma diameter or dendritic maturation in these two areas: thus, the centro-peripheral gradient is no longer apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunolocalization of tissue plasminogen activator in the diabetic and nondiabetic retina and choroid.

Retinal capillary closure is a common finding in many patients with diabetic retinopathy. The cause of this capillary occlusion is unknown. Since occlusions in microthromboembolic disease can occur because of deficiencies in tissue plasminogen activator (tPA) and since systemic tPA decreases with an increasing duration of diabetes mellitus, the immunohistochemical localization of tPA in the retinas and choroids of diabetic and nondiabetic patients was investigated. The localization of tPA was confined to arteries and arterioles in peripheral retinas from nondiabetics. Both veins and arteries were positive in these choroids. Two of three noninsulin-dependent diabetics had normal levels of immunoreactivity in their retinas, and all had normal levels of immunolocalization in their choroids. All but 2 of the 12 insulin-dependent diabetic eyes (IDDM), however, had reduced levels of retinal tPA immunoreactivity which was most pronounced in their peripheral retinas. Seven eyes from patients with IDDM had no reaction product in their peripheral retinas. Two such eyes also had reduced tPA immunoreactivity in their choroidal vessels. Some tPA-positive vessels were observed in the central retinas of these eyes, but the number of positive vessels and amount of reaction product was greatly reduced compared with eyes from nondiabetic patients. These observations suggest that IDDM patients have reduced fibrinolytic activity in their retinas, which might predispose them to thromboembolic disease.

Adult↗

[Diffusion of O2 in the normal and the ischemic retina of miniature pigs].

Transretinal PO2 profiles were recorded during normoxia and hyperoxia in normal and ischemic retinal territories in anesthetized miniature pigs using double barrelled recess type microelectrodes. In normoxia and hyperoxia the PO2 in the normal territory decreased from the inner retina and the choroid towards the mid-retina, indicating that the choroid cannot supply O2 to the whole normal retina. Preretinal and transretinal PO2 measurements in ischemic territories following a laser occlusion of a retinal branch vein demonstrated that in normoxia the direction of PO2 gradients prevents O2 diffusing from the choroid to reach the inner retina. This explains why the ischemic territories are hypoxic. In the contrary, during hyperoxia the intraretinal PO2 gradient indicates an O2 flux from the choroid to the inner retina resulting to marked preretinal PO2 increase at the affected territories. We proposed the hypothesis that in the ischemic retinas the hyperoxia does not induce a rise of the O2 consumption of the outer retina. Hence hyperoxia could be a useful tool to restore the oxygenation of the inner hypoxic retinal layers.

Animals↗

Metabolism of arachidonic acid in the retina and retinal pigment epithelium: biological effects of oxygenated metabolites of arachidonic acid.

Most of the research on AA metabolites in the eye has been concerned with the role of prostaglandins in ocular inflammations. For example, it has been postulated that cystoid macular edema (CME) is due to accumulation of prostaglandins produced after cataract surgery and that indomethacin prevents the development of CME (Tennant, 1976; Milch and Yannuzzi, 1987). It is not known if the retina is the source of these prostaglandins. Cyclooxygenase and lipoxygenase activities have been demonstrated in the retina. In this chapter, evidence is presented indicating that eicosanoids can also be involved in retinal neurotransmission and cell to cell interaction. The mammalian retina contains a relatively large amount of AA esterified to membrane phospholipids. A release of AA takes place in the retina under various experimental conditions, e.g., anoxia, K+ polarization, and light exposure. This release of AA, a prerequisite for eicosanoid syntheses, is produced by phospholipases and lipases, some of which are regulated by receptor-mediated G-proteins. Prostaglandins can act as modulators of postsynaptic responses; some can also alter the electroretinographic response, for example PGD2 selectively increases during light stimulation. An increase in LTC4 occurs in the neural retina after Ca+ ionophore stimulation and an increase in LTC4 released from retinal pigment epithelium occurs after light onset before massive shedding, suggesting an involvement of 5-lipoxygenase metabolites in the initial steps of ROS phagocytosis. Although great advances have been made regarding the function of eicosanoids in the central nervous system (of which the retina is a constitutive part), it is yet a very difficult task to determine to what extent eicosanoids are involved in the action of neurotransmitters and whether they may act as neuromodulators. This is due to the complexity of the synaptic circuitry of the retina, which makes it difficult to define their sources and physiological significance.

Animals↗

The regional distribution of vitamins E and C in mature and premature human retinas.

Vitamin E is used to ameliorate retinopathy of prematurity, but little is known about baseline vitamin E levels in retinas of premature infants or the effect of vitamin E supplementation on these levels. Vitamin E and C levels were measured in mature retinas (1 month to 73 years) and in retinas of premature infants (22 to 33 weeks of gestation). The infants fell into two groups: (1) those who survived less than 12 hr and received no vitamin E, and (2) those who survived greater than 4 days and received vitamin E supplementation. Premature infants are born with 5 to 12 percent the vitamin E levels found in mature retinas. Vitamin E levels in vascular and avascular retina of premature infants increased with gestation. Infants born greater than 27 weeks gestation and surviving at least 4 days with vitamin E supplementation demonstrated markedly elevated vitamin E levels in vascular and avascular retina when compared to supplemented infants less than 27 weeks gestation. Premature infants possessed 35-50% higher levels of retinal vitamin C than those found in mature retinas. These data demonstrate that premature infants are born with relatively low levels of retinal vitamin E, particularly in the avascular region, but contain an abundance of retinal vitamin C. These data further suggest that vitamin E supplementation results in a rapid increase in retinal vitamin E levels, particularly in infants greater than 27 weeks gestational age.

Adolescent↗

The development of retina and the optic tectum of petromyzon marinus, L. A light microscopic study.

Morphological evolution of the retina and optic tectum along the stage of ammocoete, transformation and young adult of sea lampreys (Petromyzon marinus L.) was studied using light microscopic techniques and quantitative morphometry. A retinal differentiated zone surrounding the optic nerve head with a kind of differentiated photoreceptors is present through all the stages studied until stage VI of transformation and its extension is almost unchanged since 60 mm. larve. From this length larval retina grows by extension of the lateral undifferentiated retina, that in large larvae subdivides in a lateral germinal zone and an intermediate differentiating zone more thickened were ganglion cells and the optic fibre layer differentiate early. In the largest larvae outer and inner neuroblastic layers were also recognized in these intermediate zone except in the most lateral retina. Mitotic activity was observed both in germinal and intermediate differentiating zones near the optic ventricle. The germinal zone disappears after the formation of an irideal retina in transforming stages and, with the exception of the photoreceptor layer, retinal layers were differentiated since stage III along the neural retina. The photoreceptor layer develops in the early stage VI along the retina. Adult pattern of retinal pigmentation is found in these stage. A periventricular and a lateral region were recognizable in the optic tectum of the larval period. Tectum of large larvae shows an outline of laminar organization. In the stage III of transformation the tectal lamination is the same of the young adults: the periventricular cell layer is subdivided by fibre bands and in the lateral region a stratum cellulare centralis and a stratum cellulare et fibrosum externum were distinguishable. A comparison between retinal and tectal growths was made. Most retinal and tectal growth and differentiation occurs before adult photoreceptors develop.

Aging↗