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PubMed2002

[Follow-up of proliferation of juxtapapillary retinal pigment epithelium].

PURPOSE: Bengin proliferation of the juxtapapillary retinal pigment epithelium is a rare but important tumor because it may be mistaken for a malignant lesion such as choroidal melanoma. CASE REPORT: A 9-year-old male patient consulted our clinic first in 1991 because of a reduction in visual acuity due to a tumor of the optic nerve head in the left eye. Visual acuity was 1.0 in the right eye and 0.2 in the left eye. Slit lamp examination and intraocular pressure were regular in both eyes. Kinetic perimetry showed a enlarged blind spot besides regular isopters. Funduscopy revealed a pigmented, ill-defined prominence of the optic nerve head with a mossy surface. In annual examinations were found a slowly progredient reduction in visual acuity up to 0.04 durning the last visit in January 2000 as well as a enlargement of the blind spot due to an increasing prominence and pigmentation of the optic nerve head. Because of the clincal aspect, the slowly progressive course, the enlargement of the blind spot with deterioration of vision and especially the florescein angiography, which revealed peripapillary capillary alterations with leakage, we diagnosed a proliferation of the juxtapapillary retinal pigment epithelium. CONCLUSION: The proliferation of the juxtapapillary retinal pigment epithelium can be differentiated from other pigmented tumors of the optic nerve head by its typical clinical aspect and course and especially by using flourescein angiography.

Capillary Leak Syndrome↗
PubMed1993

Cryotherapy during surgery for giant retinal tears and intravitreal dispersion of viable retinal pigment epithelial cells.

BACKGROUND: Retinal pigment epithelial (RPE) cells are a major component of contractile cellular membranes in proliferative vitreoretinopathy (PVR). Displacement of viable RPE cells into the vitreous cavity is necessary for membrane formation. This study examines the effect of cryotherapy during surgery for giant retinal tears on the dispersion of viable cells into the vitreous cavity. METHODS: A total of seven eyes undergoing vitrectomy and retinal reattachment surgery were studied. Vitreous fluid from three eyes was aspirated immediately after cryotherapy; fluid from four eyes was aspirated after scleral indentation with the cryoprobe, but without cryotherapy. Colonies of pigmented cells routinely grew in flasks inoculated with fluid from eyes treated with cryotherapy. In contrast, flasks inoculated with fluid from eyes not treated with cryotherapy contained significantly fewer viable cells. CONCLUSION: Cryotherapy performed during retinal reattachment surgery in eyes with giant retinal tears is likely to enhance intravitreal dispersion of viable RPE cells. The findings in this study suggest that possible harmful effects of cryotherapy should be evaluated further and that alternative methods of creating a chorioretinal adhesion should be considered in cases with an especially high risk of PVR.

Adult↗
PubMed1999

Matrix and the retinal pigment epithelium in proliferative retinal disease.

In their normal state, RPE cell are strongly adherent to Bruch's membrane. Certain pathological conditions such as retinal detachment cause an injury-type response (probably augmented or induced by the local accumulation of a variety of substances which modulate cell behaviour) in which RPE begin to dissociate from the membrane. This RPE-Bruch's membrane separation may be mediated by proteins with counter-adhesive properties and proteolytic enzymes, partly derived from the RPE themselves. Concomitant with the RPE disassociation, the cells begin to lose tertiary differentiation characteristics and gain macrophage-like features. When the "free" RPE arrive at the surface of the neuroretina, they may attach to or create a provisional matrix. Some of the cells adopt a fibroblast-like phenotype. This phenotype is similar to that of the dermal fibroblast during cutaneous wound repair and the fibroblastic RPE synthesise the types of matrix components found in healing skin wounds. Many of these molecules in turn further modulate the activities of the cells via several families of cell surface receptors, while the RPE continue to remodel the new matrix with a range of proteolytic enzymes. The resulting tissue (or membrane) has many of the features of a contractile scar and is the hallmark of the condition known as proliferative vitreoretinopathy (PVR). Thus the development of PVR, and the resulting tractional distortion of the neuroretina, appears to be dependent on RPE-matrix interactions. The interactions present a number of potential therapeutic targets for the management of the disorder.

Animals↗
PubMed1981

Effect of vitamin E administration on photoreceptor outer segment and retinal pigment epithelium of vitamin E deficient rats.

The photoreceptor outer segment and retinal pigment epithelium of vitamin E deficient rats given vitamin E were studied by electron microscopy. In rats fed a vitamin E deficient diet for more than 12 months, the photoreceptor outer segment did not regenerate after the administration of 400 mg of vitamin E. The retinal pigment epithelium was filled with lipofuscin granules and contained cytoplasmic organelles such as mitochondria, ribosomes and Golgi apparatus. The microvilli of the retinal pigment epithelium were long and in contact with the outer nuclear layer cells. The photoreceptor inner segment and nucleus had almost disappeared. In rats given 400 mg of vitamin E after vitamin E deficiency for 6 months, the photoreceptor outer segment showed no vesiculation and were increased in number. However, some retinal pigment epithelial cells still contained many lipofuscin granules. In conclusion, the photoreceptor outer segment and retinal pigment epithelium can be repaired in mild vitamin E deficiency by vitamin E administration, but vitamin E cannot reproduce the photoreceptor cells in nuclei of which have been broken by severe vitamin E deficiency.

Animals↗
PubMed1997

Indocyanine green angiographic evaluation of retinal pigment epithelial tears.

BACKGROUND: Although choroidal neovascularization has a recognized role in the formation of retinal pigment epithelial tears in the setting of age-related macular degeneration, there frequently was no fluorescein angiographic evidence of choroidal neovascularization in published series. METHODS: Three consecutive patients with a folded retinal pigment epithelium in a subfoveal location, which was associated with a serous macular detachment in the setting of age-related macular degeneration, were studied with intravenous fluorescein angiography and indocyanine green angiography. RESULTS: Fluorescein angiography demonstrated no well-defined choroidal neovascular membrane, although there was evidence of occult choroidal neovascularization. The folded retinal pigment epithelium blocked fluorescence. Indocyanine green angiography demonstrated placoid subfoveal hyperfluorescence consistent with choroidal neovascularization in the region of the folded retinal pigment epithelium and fibrovascular pigment epithelial detachment. Hypofluorescence was noted within the region of the retinal pigment epithelial tear. CONCLUSION: Indocyanine green angiography in our cases clearly demonstrated the presence of presumed choroidal neovascularization in the setting of retinal pigment epithelial tears secondary to age-related macular degeneration.

Aged↗
PubMedDate not supplied

Antioxidant properties of melanin in retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) is a monolayer of highly pigmented cells lining the inner aspect of Bruch's membrane. This pigmentation is due to eumelanin and a possible antioxidant role of melanin is reported here. The photo-oxidation of A2E, a constituent of RPE lipofuscin, leads to the sequential addition of up to nine oxygen atoms and/or the addition or loss of two hydrogen atoms. These photo-oxidations were investigated in the presence and absence of either calf or human RPE melanin in A2E-laden RPE cells. It was found that calf melanin was protective against the photo-oxidation of A2E, with an inhibition of oxidation of up to 50% in the case of the addition of two oxygen atoms. Calf melanin was also protective against blue light-induced damage to RPE cells. In addition this ability appears to decrease in humans as they grow older. With aging, a melanin-lipofuscin complex called melanolipofuscin forms. It is suggested that the oxidation or photo-oxidation of A2E in vivo may contribute to the age-related deterioration of the anti-oxidant role of RPE melanin and lead to various retinal disorders, such as age-related macular degeneration.

Animals↗
PubMed1999

Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration.

PURPOSE: To test the hypothesis that neovascular age-related macular degeneration is related to oxidative stress involving the macular retinal pigment epithelium. This study investigated, as a function of age, levels of enzymes that defend tissues against oxidative stress in the macular retinal pigment epithelium of human eyes with this disease. METHODS: Surgical specimens of macular choroidal neovascular membranes from eyes with age-related macular degeneration and the macular regions of whole donor eyes with neovascular age-related macular degeneration or without evident ocular disease were studied by quantitative electron microscopic immunocytochemistry with colloidal gold-labeled second antibodies. Relative levels in retinal pigment epithelium cell cytoplasm and lysosomes were determined of five enzymes believed to protect cells from oxidative stress, as well as levels of the retinal pigment epithelium marker cytoplasmic retinaldehyde-binding protein, for comparison with the enzymes. RESULTS: Copper, zinc superoxide dismutase immunoreactivity increased and catalase immunoreactivity decreased with age in cytoplasm and lysosomes from macular retinal pigment epithelium cells of normal eyes and eyes with age-related macular degeneration. Cytoplasmic retinaldehyde-binding protein immunoreactivity showed no significant relationship to age or the presence of neovascular age-related macular degeneration. Glutathione peroxidase immunoreactivity was absent from human retinal pigment epithelium cells. Both heme oxygenase-1 and heme oxygenase-2 had highly significantly greater immunoreactivity in retinal pigment epithelium cell lysosomes than in cytoplasm, differing from the much greater cytoplasmic immunoreactivity of the other proteins studied. This immunoreactivity decreased with age, particularly in the lysosomes of retinal pigment epithelium cells from eyes with neovascular age-related macular degeneration. These decreases were of borderline significance (P = .067 for heme oxygenase-1; P = .12 for heme oxygenase-2) when eyes with age-related macular degeneration were compared with normal eyes by multivariable logistic regression. CONCLUSIONS: The high heme oxygenase-1 and heme oxygenase-2 lysosomal antigen levels in macular retinal pigment epithelium cells of eyes with neovascular age-related macular degeneration suggest that oxidative stress causes a pathologic upregulation of these enzymes. Increased lysosomal disposal may indicate that the reparative functions of these enzymes are accompanied by deleterious effects, necessitating their rapid removal from the cell. The much higher heme oxygenase-1 and heme oxygenase-2 antigen levels in macular retinal pigment epithelium cells from younger individuals suggest that protective mechanisms against oxidation and, hence, presumably to the development of age-related macular degeneration, decrease with age.

Adult↗
PubMed1998

Endogenous FGF1-induced activation and synthesis of extracellular signal-regulated kinase 2 reduce cell apoptosis in retinal-pigmented epithelial cells.

Retinal-pigmented epithelial (RPE) cell survival is critical to the maintenance of the function of the neural retinal and in the development of various retina degenerations. We investigated molecular mechanisms involved in this function by assessing apoptosis in RPE cells following serum deprivation. Apoptosis induced by serum withdrawal is lower in aged RPE cells because of higher endogenous acidic fibroblast growth factor (FGF1) synthesis and secretion. These experiments examined several aspects of FGF signaling and the contribution of endogenous FGF1 to activation of the extracellular signal-regulated kinase 2 (ERK2). In aged RPE cells, FGFR1 was rapidly activated, and its autophosphorylation followed the kinetics of endogenous FGF1 secretion, before the onset of apoptosis. ERK2 phosphorylation, activity, and de novo synthesis increased at the same time. In marked contrast, no de novo JNK1 synthesis was observed. MEK1 inhibition resulted in lower levels of ERK2 activation and synthesis and higher levels of apoptosis. Treatment with neutralizing anti-FGF1 or blocking anti-FGFR1 antibodies mimics these effects. Thus, this study strongly suggests that the survival-increasing effect of FGF1 in aged RPE cells is because of an autocrine/paracrine loop in which the ERK2 cascade plays a pivotal role.

Animals↗
PubMedDate not supplied

[A hormone-sensitive stage in the development of the retinal pigment epithelium in Hunter rats with hereditary retinal dystrophy].

The sensitivity of the retinal pigment epithelium (RPE) to the melanotropic effects of alpha-MSH and dbcAMP was assayed in an organ culture of the eye scleral part in the Hunter rats with inherited retinal dystrophy. The melanin synthesis was estimated by liquid scintillation on the RPE isolated enzymatically after 48-h cultivation. One eye from every animal was cultivated in a medium without natural components and with the hormone or dbcAMP (experiment), while the other in a hormone-free medium (control). The melanin synthesis was estimated by 14C-thiouracil incorporation. The result was expressed as a cpm/microgram DNA (experiment) to cpm/microgram DNA (control) ratio. In addition, the index of labelled nuclei was determined using 3H-thymidine autoradiography in the central RPE zone of the eyes from young rats of the same litter. The experiments with alpha-MSH confirmed the earlier data according to which the RPE of the 3 day old Hunter rats were insensitive to melanotropic hormones. This was not due to defects in the cytoplasmic melanin-synthesizing system, since under the influence of dbcAMP the melanin synthesis in the RPE increases more than four-fold as compared with the control; dbcAMP stimulates also the total protein synthesis, as estimated by 3H-leucine incorporation. The RPE of the 4 day old rats proved to be sensitive to alpha-MSH: the melanin synthesis increases more than twice suggesting the healthy state of the RPE membrane melanotropic receptors. alpha-MSH also stimulates the total protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Synergistic effects of gamma interferon on inflammatory mediators that induce interleukin-6 gene expression and secretion by human retinal pigment epithelial cells.

The retinal pigment epithelial (RPE) cell is a potent regulatory cell within the retina. It helps to maintain normal retinal activity, and following gamma interferon (IFN-gamma) exposure, it may express major histocompatibility complex class II molecules and function as an antigen-presenting cell. Since interleukin-1 (IL-1) and IL-6 are potent cytokines observed in ocular inflammatory processes, we initiated studies to evaluate conditions which enable RPE cells to produce these cytokines. Cultures of human RPE cells from two eye donors were established and characterized, and enzyme immunoassays were employed to screen for IL-1 and IL-6 production. Treatment of RPE cells with lipopolysaccharide (LPS) or recombinant tumor necrosis factor alpha, IL-1, or IFN-gamma resulted in a significant level of secretion of IL-6. In contrast, treatment with recombinant epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, or transforming growth factor alpha, or LPS can dramatically augment the secretion of IL-6 by RPE cells. Thus, these inflammatory mediators can act alone or synergistically with IFN-gamma to activate RPE cells and dramatically increase the expression and secretion of IL-6. In contrast, IL-1 was not detected following stimulation with any of the above-mentioned cytokines or LPS. Characterization of IL-6 protein production by RPE cells revealed that 98% of the protein is promptly secreted by the cell, its induction is dependent upon the time and concentration of the stimulant, and the continuous presence of the stimulant is required for IL-6 production. Moreover, Western blot (immunoblot) analysis of secreted proteins revealed that IL-6 was produced in multiple molecular forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1978

Some observations in the fine structure of age changes of the mouse retinal pigment epithelium.

Age changes of the fine structure in the CF-1 mouse retinal pigment epithelium were studied from 1--24 months old. The change most characteristic of the senescence of the retinal pigment epithelium was found to be the appearance of wavy undulating 12nm wide filaments having a periodicity of about 80nm after the 12th month. In addition, the retinal pigment epithelial cells of the aging eye were found to have a marked accumulation of lysosomal dense bodies measuring about 0.3 to 1.2 micrometer in diameter especially in the apical portion of the cytoplasm. Extended and enlarged basal cytoplasmic infoldings of the retinal pigment epithelial cells were another prominent age change in the old mouse. In these basal infoldings densely fixed amorphous materials by tannic acid and very fine filaments are recognized. Age-related changes of the retinal pigment epithelial cell of the CF-1 mouse may take place as the degeneration of cytoplasmic materials, the appearance of bundles consisting of parallel undulating filaments, and the extending process of basal infolding from the choroid side.

Aging↗
PubMed1986

Chick retinal pigment epithelium exhibits glutathione requiring prostaglandin D2 synthetase activity.

Prostaglandin synthetic activity of neural retina and retinal pigment epithelium in chick retina was studied using arachidonic acid and prostaglandin H2 (intermediate prostaglandin endoperoxide) as substrates. To obtain sufficient enzyme activity in retinal pigment epithelium, cultured chick retinal pigment epithelial cells were used. Little arachidonic acid was converted into prostaglandins, and details of prostaglandin synthetic activity were not clear. The assay from prostaglandin H2 showed that: 1) preparations consisting of both neural retina and retinal pigment epithelium dissected from 7-day-old chicks have activity of glutathione-requiring prostaglandin D2 synthetase; 2) preparations consisting of only neural retina dissected from 7-day-old chicks have no activity of prostaglandin synthetase; and 3) cultured chick retinal pigment epithelial cells have high activity of glutathione-requiring prostaglandin D2 synthetase.

Animals↗
PubMed2003

Regional differences and post-mortem stability of enzymatic activities in the retinal pigment epithelium.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for the metabolism of the neural retina. As a result of dysfunction of the RPE, retinal degeneration occurs. A potential treatment for certain forms of retinal degenerations is transplantation of RPE cells. To determine optimal conditions for treatment of donor eyes before transplantation, activities of key proteases (aminopeptidase M, dipeptidylpeptidase II and IV and gamma-glutamyltranspeptidase) as indicators of RPE cell quality (viability and functional state) were measured. METHODS: Protease activities were quantified in bovine RPE cells from different regions of the eyecup, after different times of storage of the bulbi, cryopreservation of the RPE cells and in RPE cell cultures. The distribution of the activities was compared to the pigmentation of the RPE cells, the thickness of the choroid and photoreceptor density. RESULTS: Most proteases showed regional maxima. Prolonged storage of the bulbi decreased gamma-glutamyltranspeptidase and aminopeptidase M activities. Cryopreservation of the RPE cells for up to 6 weeks caused no loss in the enzymatic activities. Culture of RPE cells caused pronounced decreases in the activities of gamma-glutamyltranspeptidase and dipeptidylpeptidase IV. Storage of the bulbi at 4 degrees C for more than 50 h causes marked loss of enzymatic activities in RPE cells. CONCLUSION: The decrease in gamma-glutamyltranspeptidase activity may be especially important because the RPE is exposed to high concentrations of reactive oxygen species. Whole bulbi should be stored for less than 50 h, but isolated RPE cells may be stored at -80 degrees C for weeks. Propagation of RPE cells by culture increases cell number; this effect may be counteracted by a decrease in the function of these cells.

Animals↗
PubMed2001

Central areolar choroidal and retinal pigment epithelial dystrophy: a family report.

Central areolar choroidal and retinal pigment epithelial dystrophy (CACD) is a rare hereditary macular disease characterized by a bilateral, symmetric, and well-circumscribed solitary area in the macula with choroidal and retinal pigment epithelial atrophy. We report a family of CACD confirmed by both clinical presentation and hereditary pattern. Three members of the family were examined. They had noticed gradual visual deterioration with poor color discrimination since the fourth to fifth decades. All of them showed a bilaterally symmetric bull's-eye pattern of macular dystrophy with a sharp border of underlying large or middle choroidal vessels, which was unassociated with any surrounding lesions. Fluorescein angiography revealed a transmission window defect due to retinal pigment epithelial atrophy with remaining choriocapillaris intermingled with a hypofluorescent area of choriocapillaris atrophy. Electroretinography revealed a mild reduction in the photopic amplitude, while the scotopic response was normal. A normal electro-oculography was also noted. The family history indicated autosomal dominant inheritance. The loss of visual acuity was caused by progressive atrophy of both the retinal pigment epithelium and the choriocapillaris. It is important to detect CACD in the early stages, because this diagnosis can exert a considerable influence on a patient's subsequent life.

Aged↗