Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Retinal Pigments”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

Lecithin:retinol acyltransferase in retinal pigment epithelial microsomes.

Microsomal preparations from retinal pigment epithelium carry out phosphatidylcholine synthesis upon incubation with 1-palmitoyllysophosphatidylcholine and fatty acyl-CoA. Phosphatidylcholine synthesized in situ in this manner is an acyl donor for retinyl ester synthesis, demonstrating the existence of lecithin:retinol acyltransferase. Although acyl transfer to retinol is from the 1-position of phosphatidylcholine, the fatty acid in the 2-position is important in substrate recognition. The finding of this novel enzyme activity in retinal pigment epithelial microsomes suggests that phosphatidylcholine is the endogenous acyl donor in CoA-independent retinol esterification observed in these preparations.

Acyltransferases↗

Prolonged incubation with elevated glucose inhibits the regulatory response to shrinkage of cultured human retinal pigment epithelial cells.

Transport defects by retinal pigment epithelial (RPE) and other cells are observed in experimental models of diabetes mellitus. Recent studies have established that glucose concentration, per se, is the critical risk factor in the pathogenesis of diabetic complications. This study was designed to test whether transport alterations could be produced in the simplest model of diabetes, sustained exposure of cultured cells to a high-glucose environment. The regulatory transport responses to acute changes in cell volume were measured in order to assess the effects of glucose on a range of transport processes. Continuous lines of nontransformed human retinal pigment epithelial (hRPE) cells were grown for two weeks with either 5.6 low glucose (LG) or 26.0 high glucose (HG) mM in paired experiments. The cell volumes of suspended cells were studied in hypo-, iso- and hypertonic solutions containing the same ionic composition. Hypotonic swelling triggered a regulatory volume decrease (RVD), inhibited by reducing the chemical driving force for K+ efflux, or blocking K+ channels (with Ba2+) or Cl- channels (with NPPB). Thus, the RVD of the hRPE cells likely reflects efflux of K+ and Cl- through parallel channels. Shrinkage caused a regulatory volume increase (RVI), which was inhibited by blocking Na+/H+ (with dimethylamiloride) or Cl-/HCO3- exchange (with DIDS). Bumetanide inhibited the RVI significantly only when the K+ concentration was increased above the baseline level. Therefore, the RVI under our baseline conditions likely reflects primarily Na+/H+ and Cl-/HCO3- antiport exchange. Growth in high-glucose medium had no substantial effect on the RVD, but reduced the rate constant of the RVI by approximately 50%. The RVI was unaffected by growth in high-mannitol medium. Stimulation of protein kinase C (PKC) with DiC8 increased the RVI of HG-cells, but not of LG-cells. The DiC8-induced stimulation was bumetanide insensitive and abolished by 1 mM amiloride. Other transport effects of PKC (on the RVD) were unaltered in the HG-cells. We conclude that sustained elevation of extracellular glucose, per se, can downregulate the Na+/H+ antiport of target cells, an effect noted in streptozotocin-treated rats, and that this downregulation does not reflect interruption of the PKC-signaling pathway.

Antiporters↗

Characterization of adenylate cyclase in human retinal pigment epithelial cells in vitro.

Human retinal pigment epithelial cells in culture demonstrate adenylate cyclase activity. It is membrane-bound and modulated by GTP regulatory proteins. It is effectively activated only by beta-adrenergic agonists (L-isoproterenol greater than or equal to L-epinephrine greater than L-norepinephrine) and some prostaglandins (PGE1 and PGE2, but not PGF1 alpha). The adrenergic response appears to be mediated by beta-2 receptors. No inhibitory ligands could be demonstrated. Its characteristics, which are similar to functional adenylate cyclase complexes in other mammalian cells, and its selective and sensitive agonist responsiveness, suggest a possible physiologic role in the regulation of human retinal pigment epithelial-cell function.

Adenylyl Cyclases↗

Retinal pigment epithelium tears following verteporfin therapy combined with intravitreal triamcinolone.

PURPOSE: To detect patients with neovascular age-related macular degeneration (AMD) who experience retinal pigment epithelium tears after initial verteporfin therapy combined with intravitreal triamcinolone during early follow-up. DESIGN: Prospective interventional case series. METHODS: Forty-five consecutive patients with choroidal neovascularization (CNV) in AMD were treated with verteporfin therapy combined with 4 mg of intravitreal triamcinolone. Optical coherence tomography (OCT), visual acuity, and fluorescein angiography were performed. RESULTS: Two eyes with a predominantly classic CNV developed a retinal pigment epithelium tear. An early onset tear could be differentiated from a delayed onset tear. OCT showed an increased depth signal in areas of missing retinal pigment epithelium and a wavy, contracted, and elevated retinal pigment epithelium band. CONCLUSIONS: Retinal pigment epithelium tears can occur despite adding intravitreal triamcinolone to verteporfin therapy. OCT shows characteristic changes in the evolution of retinal pigment epithelium tears after combination therapy.

Choroidal Neovascularization↗

Cytokine regulation of nitric oxide synthase in mouse retinal pigment epithelial cells in culture.

Nitric oxide is an intercellular signaling molecule whose numerous functions include regulation of vascular tone, mediation of the cytotoxic effects of macrophages and potentiation of synaptic transmission. For some cellular functions, nitric oxide synthesis is mediated by the inducible form of nitric oxide synthase. We now show that cultured mouse retinal pigment epithelial cells exposed to interferon-gamma and lipopolysaccharide, express inducible nitric oxide synthase. The latter was detected immuno-cytochemically in interferon-gamma-lipopolysaccharide-treated retinal pigment epithelium using rabbit antiserum to a synthetic peptide of mouse nitric oxide synthase. Untreated cultures of retinal pigment epithelium or cultures treated with either interferon-gamma or or lipopolysaccharide alone were not immunoreactive. Induction of iNOS in gamma-interferon-lipopolysaccharide-stimulated retinal pigment epithelial cells was also evidenced by the presence of nitric oxide synthase enzyme activity in lysates of stimulated but not unstimulated retinal pigment epithelial cells. On immunoblots of lysates of stimulated murine retinal pigment epithelial cells, rabbit antiserum to iNOS recognized a 130-kDa protein which comigrated with the inducible nitric oxide synthase of macrophages and which was not detectable in lysates of unstimulated retinal pigment epithelial cells nor in lysates of cells treated with only interferon-gamma or lipopolysaccharide alone. Nitrite, a stable endproduct of NO formation by cells, was detectable in the culture supernatants after 18-24 hr of exposure to interferon-gamma and lipopolysaccharide, and continued to accumulate in a linear fashion for at least 96 hr. Treatment of cultured retinal pigment epithelium with interferon-gamma, lipopolysaccharide and either basic fibroblast growth factor or epidermal growth factor as third signals augmented inducible nitric oxide synthase expression as evidenced by intensified signals on immunoblots, enhanced accumulation of nitrite and increased iNOS enzyme activity. Conversely, when transforming growth factor-beta was present in the culture medium, gamma-interferon-LPS-induced expression of nitric oxide synthase and NO release were reduced. We conclude that interferon-gamma synergizes with lipopolysaccharide to induce synthesis of inducible nitric oxide synthase and production of nitric oxide by murine retinal pigment epithelium and that this induction can be modulated by basic fibroblast growth factor, epidermal growth factor or transforming growth factor-beta.

Amino Acid Oxidoreductases↗

A new model of retinal pigment epithelium transplantation with microspheres.

OBJECTIVES: To develop a 3-dimensional carrier system for subretinal transplantation of human fetal retinal pigment epithelial (HFRPE) cells and to assess their growth pattern in the rabbit subretinal space. METHODS: After a standard 3-port vitrectomy, HFRPE cells grown as microspheres on cross-linked fibrinogen were introduced into the subretinal space of rabbits. The eyes were studied at 7, 14, and 30 days after surgery by ophthalmoscopy and light microscopy. RESULTS: Ophthalmoscopically, at day 7, 11 (61%) of the 18 eyes showed radiating hyperpigmentation around the transplanted HFRPE microspheres. The results of a histological examination revealed a monolayer outgrowth of HFRPE cells, overlying host retinal pigment epithelium. The control eyes revealed a patch of chorioretinal atrophy with lymphocytic infiltration around the microspheres. CONCLUSIONS: Human fetal retinal pigment epithelial cells grown as microspheres on cross-linked fibrinogen can be successfully transplanted into the subretinal space. Cells can survive for at least 1 month and form a monolayer over the host retinal pigment epithelium cells, with a mild local inflammatory response. The difference in inflammatory responses between the eyes that underwent transplantation and the control eyes may suggest a modulating effect of the HFRPE cells on inflammation, immunity, or both. This new xenogenic model may have importance in the study of subretinal transplant cell biology and the associated immune response. CLINICAL RELEVANCE: The results of this study may be important for better understanding of the mechanisms of retinal pigment epithelium cell behavior after transplantation. The proposed model may be applicable for future clinical and experimental investigations in the area of retinal pigment epithelium transplantation.

Animals↗

Acute retinal pigment epitheliitis.

PURPOSE: To report a patient with acute retinal pigment epitheliitis examined less than 24 hours after onset of symptoms. METHOD: One day after the onset of blurred vision in her left eye, a 33-year-old woman had a best-corrected visual acuity of LE, 20/60 -2. The left eye had classic uniform golden-colored nodules in a honeycomb pattern in the foveal retinal pigment epithelium. Intravenous fundus fluorescein angiography disclosed staining of the foveal pigment epithelium. RESULTS: One month after initial examination, visual acuity was LE, 20/20, and fine subfoveal pigmentary clumping was present. CONCLUSION: The pigmentary maculopathy of acute retinal pigment epitheliitis may be nonspecific, resulting from more than one type of primary foveal inflammation.

Acute Disease↗

The polarity of the retinal pigment epithelium.

The diversity of epithelia in the body permits a multitude of organ-specific functions. One of the foremost examples of this is the retinal pigment epithelium. Located between the photoreceptors of the retina and their principal blood supply, the choriocapillaris, the retinal pigment epithelium is critical for the survival and function of retinal photoreceptors. To serve this purpose, the retinal pigment epithelium cell has adapted the classic Golgi-to-cell-surface targeting pathways first described in such prototypic epithelial cell models as the Madin-Darby canine kidney cell, to arrive at a unique distribution of membrane and secreted proteins. More recent data suggest that the retinal pigment epithelium also takes advantage of its inherent asymmetry to augment the classical pathways of Golgi-to-cell-surface traffic. As retinal pigment epithelium transplants and gene therapy represent potential cures for retinal degenerative diseases, understanding the basis of the unique polarity properties of retinal pigment epithelium cells will be a critical issue for the development of future therapies.

Animals↗

A study of photoreceptor-retinal pigment epithelium complex: age-related changes in monkeys.

Retinas of 4-, 10-, and 20-year-old monkeys were studied by light microscopy, electron microscopy, and scanning electron microscopy. Sections from the midperipheral region of every retina were selected for comparison. Although no significant differences were found between 4- and 10-year-old retinas, four major changes were found in 20-year-old monkey retinas: (i) increased number of displaced photoreceptor cells (DPC), (ii) increased number of macrophages of different morphology in subretinal space, (iii) increase in pigment granules in retinal pigment epithelium (RPE) cells, and (iv) altered morphology of Muller cells. DPC included both rods and cones. Their location and morphology depended on the stage of their displacement. These cells were usually oval or rounded in shape and were found either among the outer segments of other photoreceptor cells, having stalks extending into the outer nuclear layer, or were located in the subretinal space and had no stalk. A narrow space around the DPC stalks, indicating a change in the intercellular connection between photoreceptor cells and Muller cells, was observed. Furthermore, the Muller cells related to DPC had shortened and markedly reduced microvilli. Two types of macrophages were found in the subretinal space of aged monkey retinas. One type was similar in morphology to RPE cells. Some of these cells were noticed detaching from RPE. Other types of macrophages were nonpigmented. The modifications in RPE were closely related to the changes in the associated neuroretina. The RPE cells in aged retina were devoid of microvilli or had a few thin microvilli. The pleomorphic pigment granules were dispersed throughout the cytoplasm. These cells varied in their size, shape, and surface features. These changes could significantly alter the retinal metabolic equilibrium and may be indicative of age related degenerative processes.

Aging↗

Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: clinicopathologic correlation.

PURPOSE: To report the histopathology after retinal pigment epithelial cell transplantation and subfoveal membranectomy in age-related macular degeneration. METHODS: An 85-year-old white woman with bilateral choroidal neovascularization underwent subfoveal membranectomy combined with transplantation of a sheet of human adult retinal pigment epithelium (retinal pigment epithelium) under the foveal center in the right eye. The patient was immunosuppressed postoperatively with prednisone, cyclosporine, and azathioprine. The patient died from congestive heart failure 114 days after surgery. RESULTS: A patch of hyperpigmentation was visible at the transplant site under the foveola after surgery. Mound-like clusters of individual round, large densely pigmented cells were present in the subretinal space and outer retina in this area. There was loss of the photoreceptor outer segments and native retinal pigment epithelium in the center of the transplant bed, with disruption of the outer nuclear layer predominantly over regions of multilayered pigmented cells. Cystic spaces were present in the inner and outer retina. A residual intra-Bruchs membrane component of the original choroidal neovascular complex was present under the transplant site. CONCLUSIONS: The transplant site contained clusters of round, pigmented cells that did not form a uniform monolayer in most areas. The morphology at the transplant site is consistent with the lack of visual improvement seen after surgery in this patient.

Aged↗

Lipids of plasma, retina, and retinal pigment epithelium in Swedish briard dogs with a slowly progressive retinal dystrophy.

Reduced blood levels of long chain polyunsaturated fatty acids have been reported in humans and animals with inherited retinal degenerations. The lipid and fatty acid compositions of plasma, retina, and retinal pigment epithelium of the Swedish Briard dog, which has a very slowly progressive retinal dystrophy that is inherited in an autosomal recessive manner were analysed. The lipid class composition of the pigment epithelium was not different between affected and normal dogs; however, significant differences were found between the retinas of the two groups. Affected dogs had relatively more phosphatidylethanolamine and phosphatidylinositol and less phosphatidylcholine than normal dogs. There was no difference in the fatty acid compositions of plasma and retinal pigment epithelium between affected and normal dogs. However, the retinas of affected dogs had significantly lower levels of 22:5n-3 and 22:6n-3 and higher levels of 18:2n-6, 20:4n-6, and 22:5n-6. The total n-3 fatty acid content was significantly lower in affected retinas (P < 0.001), whereas the content of n-6 fatty acids was significantly higher in affected retinas (P < 0.001). These studies provide evidence for yet another animal model of inherited retinal degeneration with a defect in retinal polyunsaturated fatty acid metabolism. The fatty acid pattern in affected dogs resembles that seen in the retina in n-3 fatty acid deficiency.

Animals↗

Transgenic expression of IGF-1 modifies the proliferative potential of human retinal pigment epithelial cells.

PURPOSE: To induce the expression of insulin-like growth factor (IGF)-1, by using gene transfer methods, to modify the growth characteristics of human retinal pigment epithelial cells. METHODS: Human retinal pigment epithelial cells were transfected in vitro with plasmid vector pcDNA:IGF-1, which encodes an epitope-tagged human IGF-1 fusion protein and a selectable neomycin resistance gene. Transduced cells were cloned in G418 and expanded for analysis of IGF-1 transgene expression and its effect on the cell phenotype. The expression of the IGF-1 transgene in cloned cells was confirmed by reverse transcription-polymerase chain reaction and quantified by Western blot analysis. The growth characteristics of transduced clones were compared with the control by spectrophotometric and flow cytometric cell proliferation assays. RESULTS: Cloned retinal pigment epithelial cells expressed the IGF-1 transgene and secreted the IGF-1 fusion protein into the tissue culture medium. Transduced clones demonstrated a dose-dependent, enhanced ability to proliferate in low serum conditions, compared with the control. Clones that expressed moderate and high levels of the IGF-1 fusion protein were isolated and grew at a significantly faster rate and showed a statistically significant increase in the number of cells after 6 days, compared with the control (P < 0.002, paired samples, t-test). Expression of the IGF-1 transgene in synchronized clones enhanced cell cycle kinetics by increasing recruitment of the G(0)-G(1)-phase cells into the proliferative phase of the cell cycle. CONCLUSIONS: The human IGF-1 fusion protein encoded by the pcDNA:IGF-1 vector demonstrates paracrine biological activity in human retinal pigment epithelial cells in vitro. Expression and secretion of the IGF-1 transgene enhances growth characteristics in a dose-dependent manner and can modulate the proliferative potential of the retinal pigment epithelial cell.

Blotting, Western↗

Involvement of fibronectin in in vitro regeneration of retinal pigment epithelium.

Argon laser photocoagulation was placed on the confluent monolayer of cultured chick retinal pigment epithelial cells as a model of the regeneration process of retinal pigment epithelium after laser burn. The intense fibrillar net immunofluorescent pattern of fibronectin appeared on the burnt area from 2 h after the laser application, before the beginning of tissue reconstruction. Fibronectin was observed for several days, then became undetectable before the complete regeneration of retinal pigment epithelial cells. This indicates that fibronectin is involved in the early regeneration process of retinal pigment epithelium.

Animals↗

Vitamin E in human neural retina and retinal pigment epithelium: effect of age.

Vitamin E levels were measured in retina and retinal pigment epithelium from human eye bank donors of from 12-82 years of age. In comparison to an age group of 12-45 years, humans 59-82 years of age had a higher concentration of vitamin E in both retina and retinal pigment epithelium. Depending on age, the concentration of vitamin E in retinal pigment epithelium was from 4-7 times higher than in retina. Vitamin E accumulated in the human retinal pigment epithelium in an age dependent fashion, so that by 80 years it was from 3-4 times higher than in those 20 years old. The level of vitamin E in young human retinal epithelium, however, was higher than in comparable bovine tissue. The age-related increase in human tissue vitamin E levels does not appear to be affected by postmortem time.

Adult↗

Effects of photodegradation on the physical and antioxidant properties of melanosomes isolated from retinal pigment epithelium.

Melanosomes of the retinal pigment epithelium (RPE) are relatively long-lived organelles that are theoretically susceptible to changes induced by exposure to visible light. Here melanosomes were isolated from porcine RPE cells and subjected to high intensity visible light to determine the effects of illumination on melanosome structure and on the content and antioxidant properties of melanin. As compared to untreated melanosomes, illuminated granules showed morphologic changes consistent with photodegradation, which included variable reductions in electron density demonstrated by transmission electron microscopy (TEM), and particle fragmentation and surface disruption revealed by scanning electron microscopy (SEM) and atomic force microscopy. Illuminated melanosomes had lower melanin content, indicated by measures of absorbance and electron spin resonance (ESR) signal intensity, and reduced ability to bind iron, shown by chemical and ESR analyses. Compared to untreated melanosomes, ESR-spin trapping analyses further indicated that illuminated melanosomes show increased photogeneration of superoxide anion and reduced ability to inhibit the iron ion-catalyzed free radical decomposition of hydrogen peroxide. It appears therefore that visible light irradiation can disrupt the structure of RPE melanosomes and reduce the amount and antioxidant properties of melanin. Some of these changes occur in human RPE melanosomes with aging and the results obtained here suggest that visible light irradiation is at least partly responsible. The consequence of light-induced changes in RPE melanosomes may be a diminished capacity of melanin to help protect aged cells from oxidative damage, perhaps increasing the risk of diseases with an oxidative stress component such as age-related macular degeneration.

Animals↗

Characterization of monoclonal antibodies recognizing retinal pigment epithelial antigens.

PURPOSE: To purify and characterize retinal pigment epithelial proteins exhibiting uveitogenic characteristics after immunization of Lewis rats, a broad panel of monoclonal antibodies directed against retinal pigment epithelial (RPE) protein antigens, was isolated. METHODS: Bovine RPE detergent extracts were used to isolate monoclonal antibodies against RPE antigens. Species and tissue specificity within the eye was tested through immunocytochemical analysis. Western blot analysis was used to determine the molecular weight of the RPE antigens. RESULTS: Several RPE-reactive antibodies were obtained. At least four monoclonal antibodies were isolated that reacted with different RPE antigen types. Against most of the antigens more than one hybridoma cell line was isolated. Two hybridoma lines were isolated producing antibodies, which on immunocytochemical analysis showed strong reactivity with the RPE and eye muscle tissue. The latter monoclonal antibody recognizes a 32 kD protein in RPE cells. Five monoclonal antibodies recognize a protein with an apparent molecular weight of 65 kD. One cell line was isolated that produced antibodies showing an irregular reaction pattern with both iris and ciliary body. CONCLUSIONS: RPE cells, striated eye muscle and smooth muscle cells share a 32 kD antigenic protein. This antigen is present in almost all ocular epithelial cells. Based on reaction patterns on Western blot and immunocytochemical analysis, there are at least three different 65 kD RPE antigens, two of which are RPE-specific and one of which is also present in the kidney epithelium.

Animals↗

Microperoxisomes in retinal pigment epithelium.

Microperoxisomes were found to be abundant in the retinal pigment epithelium of the human, rhesus monkey, mice, rats, domestic fowl, and frog by ultrastructural histochemistry. They were rare in other cells of the retina and choroid. These organelles had a granular matrix, ranged in diameter from 0.15 mum to 0.30 mum, and were bound by a single tripartite membrane which often maintained slender connections with the smooth endoplasmic reticulum and other microperoxisomes. They exhibited a positive reaction (electron opaque product) following incubation in diaminobenzidine and H2O2 for the demonstration of the peroxidatic activity of catalase (Novikoff et al., J. Histochem. Cytochem. 20: 1006, 1972). The reaction was inhibited by: (1) aminotriazole; (2) dichlorophenol-indophenol; (3) preheating at 95 degrees C.; or (4) elimination of H2O2. Microperoxisomes, like the well-known peroxisomes (microbodies) of liver cells have been inplicated in various aspects of lipid metabolism and the detoxification of H2O2. We demonstrated for the first time that microperoxisomes respond to drug-induced changes in lipid metabolism, as previously shown for peroxisomes. Nafenopin is a recently utilized drug which greatly decreases serum lipids, increases hepatic catalase activity, and induces an increased size and number of hepatic peroxisomes. Black, beige, albino, and obese mutant mice of the C57BL/6J strain treated with nafenopin for several weeks showed a two- to threefold increase in the number of microperoxisomes in the retinal pigment epithelium. Microperoxisomes of the retinal pigment epithelium may be involved in the transport, storage, and rapid turnover of lipids associated with the maintenance of photoreceptor outer segment disc membranes.

Adult↗