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PubMed1993

Glutamate and taurine uptake by retinal pigment epithelium during rat development.

1. The rat retinal pigment epithelium accumulated glutamate and taurine by saturable, temperature and Na(+)-dependent mechanisms. 2. Glutamate and taurine showed high and low affinity transport systems, with a Km of 30 microM and 80 microM, respectively. 3. The transport rates of both amino acids decreased during maturation of retinal pigment epithelial cells while their kinetic characteristics were not modified. 4. The results suggest an involvement of the retinal pigment epithelium in the regulation of glutamate and taurine levels in the neural retina and support its role as part of the blood retinal barrier.

Animals↗
PubMed2003

Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) of the eye transports water and lactate ions in the direction from retina to choroid. The water transport is important in maintenance of retinal adhesion and the transport of lactate ions serves to regulate the lactate levels and pH of the subretinal space. This study investigates by means of a non-invasive technique the mechanism of coupling between transport of H(+), lactate ion, and water in the monocarboxylate transporter (MCT1) located in the apical (retinal) membrane of a mammalian RPE. Primary cultures of porcine RPE cells were grown to confluence and placed in a perfusion chamber in which the solution facing the retinal membrane could be changed rapidly. Two types of experiments were performed: Changes in cell water volume were measured by self-quenching of the fluorescent dye Calcein, and changes in intracellular pH were measured ratiometrically using the fluorescent dye BCECF. In lactate-free solutions, mannitol addition to the retinal bath caused intracellular acidification and cell shrinkage, given by a single osmotic water permeability of 1.2+/-0.1 x 10(-4)cmsec(-1) (osmoll(-1))(-1). In solutions containing 50 mmoll(-1) lactate, however, the mannitol-induced cell shrinkage was faster and the cells alkalinized. These effects were not linear functions of the magnitude of the imposed osmotic gradients: Both volume effects and changes in intracellular pH showed apparent saturation with increasing gradients. Abrupt isosmotic replacement of Cl(-) with lactate in the concentration range from 3 to 50 mmoll(-1) caused an immediate cell swelling as well as an immediate intracellular acidification; both effects showed apparent saturation with increasing lactate concentration. The K(m) values were: 11+/-2 mmoll(-1) for the water fluxes and 13+/-4 mmoll(-1) for the H(+) and lactate fluxes. The data suggest that H(2)O is cotransported along with H(+) and lactate ions in MCT1 localized to the retinal membrane. The study emphasizes the importance of this cotransporter in the maintenance of water homeostasis and pH in the subretinal space of a mammalian tissue and supports our previous study performed by an invasive technique in an amphibian tissue.

Animals↗
PubMed1992

Response of the retinal pigment epithelium to selective photocoagulation.

Multiple short argon laser pulses can coagulate the retinal pigment epithelium selectively, while sparing the adjacent neural retina and choroid; in contrast, continuous-wave laser irradiation typically damages the neural retina and choroid. The healing response to selective photocoagulation of the retinal pigment epithelium was studied in rabbits during a period of 4 weeks. The lesions were never visible ophthalmoscopically. During the healing period, the epithelium was reformed by a single sheet of hypertrophic retinal pigment epithelial cells. In contrast to continuous-wave photocoagulation, only minimal inflammatory response was found. Retinal pigment epithelial cells showed clear signs of viability, eg, phagocytized outer segments. The local edema in the photoreceptor layer and subretinal space found in the early stage disappeared when the blood-retinal barrier was reestablished. The choriocapillaris remained unaffected. No subsequent damage to the photoreceptors was found. This type of photocoagulation may be useful for retinal pigment epithelium-related diseases, eg, diffuse diabetic macular edema.

Animals↗
PubMed1976

Primary retinal degeneration: evidence of normal phagocytosis in the retinal pigment epithelium.

In rats with primary retinal degeneration, lens extraction combined with total retinal detachment provided a model for injection of a tracer of colloidal carbon into the subretinal space. Electron microscopy and acid phosphatase cytochemistry were subsequently used to analyze the ingestion of tracer by the retinal pigment epithelium. It was found that the attachment, ingestion, and digestion phases of the phagocytic process were apparently preserved. From this evidence it is suggested that there is no lack of phagocytic power in the retinal pigment epithelium of affected rat strains.

Acid Phosphatase↗
PubMed2006

Retinal pigment epithelial tear following intravitreal pegaptanib sodium.

PURPOSE: To report two cases of a retinal pigment epithelial tear after intravitreal injection of pegaptanib sodium. To our knowledge, this is the first report of this finding after intraocular antivascular endothelial growth factor therapy. DESIGN: Observational case reports. METHODS: Two patients presented with occult choroidal neovascularization and associated serous pigment epithelial detachment that was a result of age-related macular degeneration. Both patients were treated with an intravitreal injection of pegaptanib sodium. RESULTS: One patient developed a retinal pigment epithelium tear one week after the intravitreal injection. The second patient developed a retinal pigment epithelium tear eight weeks after treatment. CONCLUSIONS: Although these cases may represent natural history, there should be a high index of suspicion for retinal pigment epithelium tears in patients who report significant visual deterioration after intravitreal injection of pegaptanib sodium. Further studies are needed to determine whether angiographic subtypes of choroidal neovascular membranes are more susceptible to developing retinal pigment epithelium tears after treatment with antivascular endothelial growth factor agents.

Aged↗
PubMed2005

A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells.

Human retinal pigment epithelium (HRPE) cells are important in maintaining the normal physiology within the neurosensory retina and photoreceptors. Recently, transplantation of HRPE has become a possible therapeutic approach for retinal degeneration. By negative immunoselection (CD45 and glycophorin A), in this study, we have isolated and cultivated adult human bone marrow stem cells (BMSCs) with multilineage differentiation potential. After a 2- to 4-week culture under chondrogenic, osteogenic, adipogenic, and hepatogenic induction medium, these BMSCs were found to differentiate into cartilage, bone, adipocyte, and hepatocyte-like cells, respectively. We also showed that these BMSCs could differentiate into neural precursor cells (nestin-positive) and mature neurons (MAP-2 and Tuj1-positive) following treatment of neural selection and induction medium for 1 month. Furthermore, the plasticity of BMSCs was confirmed by initiating their differentiation into retinal cells and photoreceptor lineages by co-culturing with HRPE cells. The latter system provides an ex vivo expansion model of culturing photoreceptors for the treatment of retinal degeneration diseases.

Bone Marrow Cells↗
PubMed2001

Thinning and small holes at an impending tear of a retinal pigment epithelial detachment.

BACKGROUND: A tear of a retinal pigment epithelial detachment (PED) suddenly exposes a large area of bare Bruch's membrane. We report here the case of a patient whom we observed during the gradual, spontaneous development of a PED tear. METHOD: A 5.25-year case study of a 67-year-old woman with bilateral serous PEDs. RESULTS: Retinal pigment epithelial (RPE) thinning or small holes were seen along the PED margin in both eyes. Fluorescein angiograms showed intense hyperfluorescence without leakage, and indocyanine green angiography showed choroidal vessels through regions of RPE thinning or small holes. Optical coherence tomographs showed an interruption of a hyperreflective band corresponding to retinal pigment epithelium. A typical tear of the PED ensued later. CONCLUSION: Multiple, small regions of RPE thinning or holes along the margin of PED can be a sign of an impending PED tear.

Aged↗
PubMed1991

Retinoic acid promotes density-dependent growth arrest in human retinal pigment epithelial cells.

After retinal detachment the retinal pigment epithelium (RPE) undergoes a striking phenotypic change. It becomes dedifferentiated, proliferates to form multilayered colonies, and migrates into the subretinal space. These processes are important because they have been implicated in proliferative vitreoretinopathy and poor visual recovery after retinal reattachment; however the mechanisms by which they occur are unknown. In this study, the effect of retinoic acid on RPE cell morphology and growth in culture was examined. Cells grown in the presence of 1 microM retinoic acid do not exhibit cellular overgrowth and maintain characteristics associated with the morphologic appearance of mature RPE cells in vivo. Growth curves and 3H-thymidine incorporation suggest that retinoic acid inhibits RPE cell growth primarily after the cells have reached confluence. It may act by promoting density-dependent growth arrest. Dibutryl cyclic adenosine monophosphate also inhibits RPE cell growth and 3H-thymidine incorporation, but has little effect on cell morphology. However, in combination with retinoic acid it appears to have an additive effect on inhibition of cell growth and maintenance of a morphology like RPE in vivo. Retinoids have been demonstrated to modulate the growth and differentiation of several cell types. They are usually present in high levels in RPE cells. They become depleted in RPE in culture and such depletion may also occur in vivo after retinal detachment. This could play a role in the phenotypic alteration of RPE that occurs in association with retinal detachment.

Bucladesine↗
PubMed1995

Lipofuscin of the retinal pigment epithelium: a review.

Accumulation of lipofuscin is one of the most characteristic features of ageing observed in retinal pigment epithelial (RPE) cells. The lipofuscin found in RPE cells differs from that of other body tissues due to the fact that it is mainly derived from the chemically modified residues of incompletely digested photoreceptor outer segments. It is a heterogeneous material composed of a mixture of lipids, proteins, and different fluorescent compounds, the main fluorophore of which has recently been identified as a derivative of vitamin A. Research interest has variously focussed on the roles of age, light damage, free radicals, antioxidants, visual pigments, retinal locus, lysosomal enzymes, and pigmentation on lipofuscin formation, as well as the effects of lipofuscin on RPE cell function and causation of retinal disease. This article reviews the recent advances in knowledge of the composition, origin, and possible deleterious effects of RPE cell lipofuscin.

Aging↗
PubMed1975

Partial purification and properties of cathepsin D in the retinal pigment epithelium.

Cathespin D from the retinal pigment epithelium of bovine eyes was purified about 25-fold from a crude extract of retinal pigment epithelium by acid treatment, ammonium sulfate fractionation, and Sephadex G-200 column chromatography. The purified enzyme hydrolyzed bovine serum albumin optimally at pH values close to 4.0. Exposure of the enzyme to 60 degrees C. for 2 minutes resulted in 50 per cent inactivation of the activity. The enzyme activity was completely inhibited by 0.1 microgram per milliliter of pepstatin, slightly inhibited by trasylol, and not affected by soybean trypsin inhibitor. The apparent molecular weight of cathepsin D was estimated to be about 60,000 by gel filtration on Sephadex G-200.

Animals↗
PubMed1996

Effect of a somatostatin analog (octreotide acetate) on the growth of retinal pigment epithelial cells in culture.

PURPOSE: Proliferative vitreoretinopathy is a serious complication of retinal detachment surgery in which retinal pigment epithelial cells abnormally proliferate within the vitreous cavity and under the retinal surface. Octreotide acetate, a somatostatin analog, has been shown to inhibit the cellular proliferation of a variety of cell types. The aim of this study was to investigate the effect of octreotide acetate on the growth of rabbit retinal pigment epithelial cells in culture. METHODS: Retinal pigment epithelial cells were isolated from rabbits and maintained in culture. Cells were exposed to standard media or media supplemented with octreotide acetate 10(-4) M to 10(-12) M for five days. Each concentration of octreotide acetate was tested in quadruplicate. RESULTS: Exposure of rabbit retinal pigment epithelial cells to octreotide acetate significantly inhibited proliferation with a peak effect at 10(-8) M. The effect of octreotide is biphasic with higher and lower concentrations having less effect than 10(-8) M. CONCLUSIONS: This study suggests that octreotide acetate may be useful in the treatment of proliferative vitreoretinopathy; however, the optimum therapeutic dose range for this drug may be narrow.

Animals↗
PubMed1993

A comparison of phagocytosis by the retinal pigment epithelium in normal and delayed amelanotic chickens.

The retinal pigment epithelium (RPE) performs a critical role in maintaining the integrity and renewal of the retinal system by clearing the shed photoreceptor outer segment debris through the process of phagocytosis. If phagocytosis is impaired, accumulation of the debris occurs leading to the degeneration of the retina. Phagocytosis, measured by polyvinyl toluene bead uptake is a normal cell activity exhibited by the embryonic retinal pigment epithelium even before complete differentiation of the neuronal layers. It is significant that embryonic pigment epithelium from either normal or delayed amelanotic (DAM) strain is competent in the process of non-specific particle uptake. In normal chickens non-specific phagocytic activity is observable as early as embryonic day 9 and continues through the rest of the developmental period and throughout adult life. The retinal pigment epithelium in DAM chickens exhibits early phagocytic activity at embryonic day 9 and then through day 16, but by day 19 this function is lost. This loss of phagocytic capacity in RPE of the DAM strain precedes and may be instrumental in the gradual retinal degeneration exhibited by these animals. Specific phagocytosis of rod outer segments (ROS) was examined in 4-week-old post-hatch normal and DAM RPE. Phagocytosis of ROS was greatly reduced in DAM RPE implying that the defect in the DAM is expressed in non-specific and specific phagocytosis. This study indicates that the DAM retinal system can now serve as an alternative and comparative model for studying different aspects of retinal degeneration.

Animals↗
PubMed1986

Investigation and prognosis in the retinal pigment epitheliopathies.

Eighty-three patients with retinal pigment epitheliopathy have been identified from the photographic and fluorescein records of the Tennent Institute of Ophthalmology in Glasgow. Many have been brought back for follow-up assessment. Twenty-seven patients had placoid lesions, 22 geographic lesions and 15 a condition which we propose to rename the 'not ocular histoplasmosis' (NOH) syndrome. Patients with placoid lesions could be divided into typical acute multifocal placoid pigment epitheliopathy (AMPPE), where the long-term visual prognosis was poor because of recurrent disease leading to extensive areas of atrophy, and acute diffuse placoid pigment epitheliopathy which seemed to be self-limiting. No consistent evidence of viral or immunological abnormality was found in either group of patients. Geographic lesions appeared to result either from a coalescence of focal lesions or from a slow (serpiginous) spread from a single focus. Four patients with helicoid atrophy lost central vision from disciform lesions. Seven patients had pigment epithelial disorder associated with sarcoidosis. The pigment epithelial disease was unresponsive to systemic corticosteroid therapy and tended to be complicated by disciform lesions. Disciform lesions may occur in any type of pigment epitheliopathy, as may serous retinal detachment or pigment epithelial detachment. A technique for the biopsy of choroid and retinal pigment epithelium is described. This may lead to a better understanding of these disorders.

Eye Diseases↗
PubMed2005

Macular translocation with 360 degrees retinotomy for retinal pigment epithelial tear.

PURPOSE: To report a case of retinal pigment epithelial tear treated by macular translocation with 360 degrees retinotomy. METHODS: Interventional case report. A 75-year-old woman with neovascular age-related macular degeneration and retinal pigment epithelial tear underwent macular translocation with 360 degrees retinotomy and silicone oil tamponade. After 3 months, pars plana vitrectomy, silicone oil removal, and muscle surgery were performed. RESULTS: Twenty-two months after macular translocation surgery, the visual acuity of the patient had improved to 20/50 (preoperative 20/200). No proliferative vitreoretinopathy or recurrence of the choroidal neovascularisation was observed. CONCLUSIONS: Macular translocation surgery with 360 degrees retinotomy can improve vision in retinal pigment epithelial tear secondary to neovascular age-related macular degeneration.

Aged↗
PubMed1993

Expansion of the retinal pigment epithelium in experimental myopia.

Expansion of the retinal pigment epithelium was studied in neonatal chicks after one or two weeks of unilateral form vision deprivation to investigate altered ocular growth mechanisms in this experimental model of myopia. The area of individual retinal pigment epithelial (RPE) cells, measured in tangential sections, was greater in myopic eyes than in contralateral control eyes at both times. The mean RPE cell area in myopic eyes increased to the same extent as the area of the retinal pigment epithelium as a whole. In control eyes between one and two weeks, RPE cell expansion occurred predominantly in the periphery; in myopic eyes, it occurred more generally across the epithelium but was less pronounced in the temporal region. Given the absence of detectable mitotic figures in control and myopic eyes, expansion of the epithelial layer is attributable to passive stretch or growth of existing cells. Whether scleral growth or stretch occurs selectively beneath the areas of more pronounced RPE cell expansion is unknown.

Animals↗
PubMed1994

Immunocytochemical analyses of distributions of Na, K-ATPase and GLUT1, insulin and transferrin receptors in the developing retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) is unique in that Na,K-ATPase is predominantly localized on its apical surface. We studied the distributions of Na,K-ATPase and glucose transporter GLUT1, insulin and transferrin receptors in developing rat RPE cells immunocytochemically. Na,K-ATPase, first detected in 17-day-old embryonic eyes, was already distributed predominantly on the apical surface. This reversed distribution of Na,K-ATPase was maintained throughout their life. Insulin receptor and transferrin receptor were distributed exclusively on the basolateral surface. By quantitative immunogold electron microscopic technique we found that glucose transporter GLUT1 is distributed almost equal in amount on both the apical and basolateral surfaces of RPE cells, thus presumably constructing an efficient pathway for glucose transport from the choriocapillaries to the neural retina through the blood-retinal barrier. These results suggest that in the RPE cells the intrinsic basolateral plasma membrane proteins are sorted out at least in three different ways.

Animals↗
PubMed2001

Effect of Ca(2+)-free and Mg(2+)-free BSS Plus solution on the retinal pigment epithelium and retina in rabbits.

PURPOSE: To determine whether intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus (Alcon Laboratory, Fort Worth, Texas) solution alters the adhesiveness between the retinal pigment epithelium and the retina of rabbits. METHODS: Thirty-four eyes of 34 Dutch pigmented rabbits underwent lensectomy and vitrectomy. Subsequently, the vitreous cavity of 24 eyes was irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 10 or 20 minutes. The other 10 eyes were irrigated with BSS Plus solution for 20 minutes as controls. To determine the adhesiveness between the retinal pigment epithelium and retina, a retinal detachment was produced in 12 of the 34 eyes. The apical surface of the retinal pigment epithelium and the photoreceptor outer segments were examined by scanning electron microscopy. Retinal physiology was assessed by electroretinography and retinal morphology by light microscopy. RESULTS: After retinal detachment was produced, the number of cone sheaths on the apical surface of the retinal pigment epithelium after irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes (33 +/- 15, mean +/- SD) was significantly less than the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after irrigation with BSS Plus solution for 20 minutes (120 +/- 50) or the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after 10 minutes of irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution (115 +/- 49; P =.02). The b-wave amplitudes in the eyes irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes were depressed compared with the b-waves in eyes irrigated with BSS Plus solution for 20 minutes on the first postoperative day (P =.03). After the third postoperative day, there was no significant difference in the b-waves (P >.06). Light microscopy demonstrated no morphologic abnormalities after the use of both solutions. CONCLUSIONS: Intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes altered the adhesion between the retinal pigment epithelium microvilli and retinal outer segments and made the creation of retinal detachment less traumatic. These results suggest that Ca(2+)-free and Mg(2+)-free BSS Plus solution may be of clinical value for the creation of an intentional retinal detachment for foveal translocation surgery.

Animals↗
PubMed1995

Indocyanine green videoangiographic findings in detachment of the retinal pigment epithelium.

BACKGROUND: Several forms of retinal pigment epithelial detachment have been reported. The authors used indocyanine green (ICG) videoangiography, which is useful to study the choroidal vasculature and Bruch membrane, to study pigment epithelial detachments. METHODS: Ninety-eight pigment epithelial detachments in 75 eyes were classified based on the appearance of choroidal neovascular membranes or late phase findings of ICG videoangiography done at the initial examination. The authors also followed the evolution of 51 such detachments not associated with choroidal neovascularization (CNV). RESULTS: Sixty-four pigment epithelial detachments without CNV were divided into five groups. Among eyes with pigment epithelial detachments that showed intense hyperfluorescence, all except one of the patients had both eyes involved and had several pigment epithelial detachments, sometimes with exudative retinal detachments. Weak hyperfluorescence was observed more often in younger patients. During follow-up of eyes with pigment epithelial detachments that showed irregular hypofluorescence, a neovascular membrane developed in one eye, microrips developed in four eyes and retinochoroidal folds in one eye. Most eyes that showed irregular hyperfluorescence developed atrophy of the retinal pigment epithelium. In 34 pigment epithelial detachments with CNV, either irregular hypofluorescence or absence of fluorescence was observed in areas that corresponded to the pigment epithelial detachment. CONCLUSION: The intense hyperfluorescence is thought to be due to the accumulation of protein-rich fluid within the pigment epithelial detachment. Most pigment epithelial detachments that showed weak fluorescence probably represent variants of central serous choroidopathy. Pigment epithelial detachments that showed irregular hypofluorescence or hyperfluorescence were associated with age-related macular degeneration, and the former was correlated closely with CNV. Close follow-up therefore is recommended for eyes with pigment epithelial detachments that show irregular hypofluorescence.

Adult↗