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PubMed1993

A Na+/Ca2+ exchange mechanism in apical membrane vesicles of the retinal pigment epithelium.

The retinal pigment epithelium (RPE) lying between the neural retina and the choroid, performs as a transport organ for solutes and water between the choriocapillaries and the subretinal space. It also has the function to maintain the microenvironment of photoreceptors including the regulation of calcium ions during light or dark adaptation. In order to further elucidate the transport functions of the RPE, apical membranes were isolated from RPE by differential precipitation with divalent ions. In this work bovine tissues were used as well as elasmobranch tissues. For the latter, we have already purified and characterized membrane vesicles in a previous paper. Na(+)-K(+)-ATPase, alkaline phosphatase, and 5'-nucleotidase, which are marker enzymes of the apical membrane, were highly enriched in the final membrane fraction. The majority of the fraction consists of right side out vesicles. The fluorescent indicator for sodium, SBFI, or the calcium specific indicator, Fura-2, were pre-loaded into the apical membrane vesicles of RPE of either dogfish eyes or bovine eyes. When an outwardly-directed Ca2+ gradient was formed across the vesicular membranes, the Ca2+ influx was also enhanced by 136% for dogfish RPE and 167% for bovine RPE. This Na+ gradient dependent Ca2+ influx was blocked by bepridil, an antiarrhythmic agent which is a Na+/Ca2+ exchanger inhibitor. These results indicate that a Na+/Ca2+ exchanger is present in the apical membrane of bovine and dogfish RPE.

Animals↗

PubMed2001

Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells.

Retinal pigment epithelial (RPE) cells transport a variety of solutes, but the capacity of human RPE cells to transport drugs and xenobiotics is not well understood. As an initial step to address this issue, we have examined human RPE transport of verapamil. Transport of [3H]verapamil was measured in two human RPE cell lines (RPE/Hu and ARPE-19) grown to confluence on 12-well culture plates. Verapamil uptake by RPE/Hu cells was highly concentrative, reaching cell-to-medium ratios as high as 42 by 1 h. Uptake was saturable, with an apparent K(m) of 7.2 microM. Verapamil uptake decreased in the presence of metabolic inhibitors, low temperature, and organic cations, including quinidine, pyrilamine, quinacrine, and diphenhydramine. However, other organic cations, including tetraethylammonium and cimetidine failed to inhibit. Verapamil uptake was also inhibited by the cationic antiglaucoma drugs diltiazem, timolol, and propranolol. Verapamil uptake was insensitive to changes in membrane potential. However, transport was markedly altered by changes in pH. Decreasing external pH inhibited uptake, whereas efflux was stimulated. Intracellular acidification via NH4Cl prepulse also stimulated uptake. Identical findings were obtained using the commercially available cell line ARPE-19. In view of its unique specificity, the RPE cell verapamil transporter described above is a novel, heretofore undescribed, organic cation transporter, distinct from the known members of the OCT family of organic cation transporters.

Algorithms↗

PubMed1992

Mitochondrial superoxide dismutase in mature and developing human retinal pigment epithelium.

Human retinal pigment epithelium (RPE) contains two genetically distinct forms of superoxide dismutase (SOD) enzymes that scavenge harmful superoxide anions. Biochemical and immunochemical techniques were used to compare levels of copper-zinc- and manganese-containing forms of SOD (CuZn-SOD and Mn-SOD) in human adult and fetal RPE cells. It was found that Mn-SOD activity was higher in adult than fetal RPE cells, both in vivo and in vitro. Immunolocalization of Mn-SOD in cultured RPE cells showed a greater reactivity in the mitochondria of the adult cells. Primary cultures of adult RPE contained cells with various patterns of mitochondria as shown by immunolabeling for Mn-SOD. Adult RPE cells were more resistant to the effects of a superoxide generator, paraquat, which appeared to disrupt mitochondrial integrity as judged by staining with rhodamine 123. These results suggest that high levels of Mn-SOD protect mitochondria from oxidative damage that probably occurs with aging in the RPE.

Aged↗

PubMed1990

Glucose uptake, hexose monophosphate shunt activity, and oxygen consumption in cultured human retinal pigment epithelial cells.

Retinal pigment epithelium (RPE) was isolated from human donors with no known eye disease and normal-appearing fundi and was grown in culture. Population doubling times were measured for fifth passage RPE cells; the mean was 2.25 +/- 0.75 days and showed a correlation with the age of the donor. Metabolic studies were performed by perfusing the cells with 1-[13C]-D-glucose and monitoring the perfusate with magnetic resonance spectroscopy. Glucose uptake was 10.5 +/- 3.3 nmoles/min/mg protein. Lactate production from glucose was 20.0 +/- 5.00 nmoles/min/mg protein. The percentage of glucose through the hexose monophosphate shunt was 21 +/- 2%. Oxygen (O) consumption was measured at 20.1 +/- 4.1 nmoles O/min/mg endogenous and 14.5 +/- 4.8 nmoles O/min/mg with 10 mM glucose. These cells exhibit high rates of lactate production concomitantly with high oxygen consumptions and high flux through the hexose monophosphate shunt.

Cell Division↗

PubMed1989

Furosemide-sensitive Cl transport in bovine retinal pigment epithelium.

Bovine retinal pigment epithelium (RPE)-choroid explants were sealed in an Ussing chamber. Typical preparations produced a transepithelial voltage (Ve) of 12 mV (retina side positive) and had an electrical resistance (R) of 300 ohm-cm2. These values can be attributed to the RPE. Furosemide and ouabain reduced the Ve without affecting R when applied to the apical side of the RPE, but had no effect upon Ve and R when applied to the choroidal side. Acetazolamide had no effect upon Ve and R when applied to either side of the tissue. In Cl-free medium, ouabain reduced Ve without affecting R, while furosemide had no effect upon Ve and R. In Na-free medium, ouabain and furosemide had no effect upon Ve and R. Unidirectional isotope flux studies performed under open circuit conditions showed a net retina-to-choroid Cl flux that was abolished by furosemide. These results indicate that bovine RPE possesses a furosemide-sensitive Cl transport system.

Animals↗

PubMed1986

Membrane receptors for retinol-binding protein in cultured human retinal pigment epithelium.

The retinal pigment epithelium (RPE) is responsible for transport of retinol from the choroidal circulation to the photoreceptors. In the intact eye, this process is mediated by membrane receptors for plasma retinol binding protein (RBP) distributed basolaterally on the RPE cells. We have shown that cultured human RPE expresses this receptor. A binding curve exhibiting saturation was generated by incubating enzymatically detached epithelial sheets with increasing concentrations of 125I-labelled RBP. 125I-RBP binding experiments also show that the receptor is expressed at a high level in first passage subcultures, suggesting de novo synthesis, and that basally oriented receptors predominate over those associated with the apical surface, reflecting the polarization characteristic of RPE in vivo. Cultured RPE can internalize 3H-retinol carried by RBP, resulting in synthesis of labelled retinyl palmitate. Production of labelled retinyl ester is competitively inhibited when incubations include an excess of holo-RBP containing non-radioactive retinol. These results indicate that RBP not only binds to the receptor specifically, but also that this interaction is functional, effecting uptake of retinol by the RPE cells. The expression of this property of differentiated RPE favors the use of cultured RPE as a model system for studying vitamin A transport and metabolism.

Adolescent↗

PubMed1986

Light-microscopical analysis of focal adhesions of retinal pigmented epithelial cells.

Retinal pigmented epithelial (RPE) cells from eyes of chick embryos form colonies in vitro in which cells at the periphery of the colony are unpigmented, undifferentiated, and well spread, while those in center of the colony are cuboidal, polygonal, and pigmented, and resemble RPE cells in vivo. The differentiated RPE cells in the center of the colony display predominantly cell-cell adhesiveness, and their microfilaments are organized in compact, circumferential rings. Undifferentiated RPE cells from the edge of the colony, in contrast, display predominantly cell-substratum adhesiveness and have numerous stress fibers spanning their cytoplasm. The well-spread RPE cells adhere to the substratum with focal contacts and unusually large focal adhesions. The focal adhesions which are typical of the spread chick RPE cells in vitro consist of several closely apposed focal contacts, arranged in a parallel fashion, which are often coalesced with each other along their sides. They occur at the termini of prominent microfilament bundles which contain F-actin and tropomyosin along their entire length. Myosin, which is also present in these bundles, however, is less abundant than actin and tropomyosin in the terminal, focal adhesion-associated parts of these bundles. On the other hand, myosin is more abundant than actin and tropomyosin outside the microfilament bundles in the bulk of the cytoplasm. Both focal adhesions and termini of microfilament bundles coincide with the restricted regions where high concentrations of vinculin, an adhesion-specific protein, are found. In contrast, an actin binding protein, spectrin, is distributed fairly uniformly throughout the entire cortex of RPE cells, and, unlike vinculin, does not seem to participate in the binding of microfilament bundles to the plasma membrane. Although extracellular matrix components laminin, fibronectin, and heparin sulfate proteoglycan are produced and deposited by the more differentiated RPE cells in the center of the colony, heparan sulfate proteoglycan has not been detected along the surface of the flat, undifferentiated RPE cells near the edge of the colony, while both laminin and fibronectin are present in very low amounts, the former along their ventral, and the latter along their dorsal cell surfaces. These data are discussed from a point of view that the formation of highly adhesive membrane-cytoskeleton complexes of the focal type in the spread, undifferentiated RPE cells is brought about by exposure of the cells to the rigid, unyielding substrata, such as glass or plastic.(ABSTRACT TRUNCATED AT 400 WORDS)

Actin Cytoskeleton↗

PubMed1998

In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch's membrane.

Retinal pigment epithelium transplantation has been proposed as adjunctive treatment for age-related macular degeneration following surgical excision of choroidal neovascular membranes. The goal of this study was to develop a model to evaluate retinal pigment epithelium transplantation onto human Bruch's membrane in vitro. We investigated the ability of cultured fetal human retinal pigment epithelium to colonize human cadaver Bruch's membrane, determined the incubation time needed to form a monolayer and to exhibit apical microvilli and tight junctions, and assessed the production of basement membrane. Freshly enucleated (less than 48 hours old) human eyes were cut through the pars plana, and the anterior segment, vitreous, and retina were removed. The native retinal pigment epithelium was debrided with a surgical sponge. Bruch's membrane and choroid at the macula were trephined with a 7.0 mm diameter trephine and then incubated with 1/2 ml of Dulbecco's modified Eagle's medium +15% fetal calf serum+basic fibroblast growth factor (1 ng ml-1), and fetal human retinal pigment epithelium at a concentration of 242,000 cells ml-1. Specimens were incubated for 1, 4, 6, 8, 12, or 24 hours. The specimens were fixed in half strength Karnovsky's fixative, processed, and analysed with scanning and transmission electron microscopy. The retinal pigment epithelium covered the debrided macular specimens to different degrees at different incubation times. After 1 hour, the cells started to attach and flatten (median percent coverage: 78%). The extent of Bruch's membrane coverage by fetal retinal pigment epithelium varied greatly between specimens. After 4-6 hours, the cells covered the entire debrided surface in a monolayer (median percent coverage: 97.2% at 4 hours, 99.8% at 6 hours). Tight junctions were observed, and the cells had few apical microvilli. The lateral cell borders were obliquely oriented with respect to Bruch's membrane, and the nuclei were elongated, exhibited prominent nucleoli, and were oriented parallel to Bruch's membrane. After 6-8 hours, cells started to become hexagonal (median percent coverage at 8 hours: 99.97%). Cells attached to the inner collagenous layer tended to be flatter than cells attached to residual native basement membrane. At 12 and 24 hours, expression of hexagonal shape, tight junctions, and apical microvilli were observed more frequently (median percent coverage: 99.87% at 12 and 100% at 24 hours). No newly formed basement membrane was observed at these time points. In separate experiments comparing attachment in the presence and absence of native RPE basement membrane, the presence of native retinal pigment epithelial basement membrane promoted the early attachment of the cells and more rapid expression of normal morphology. This in vitro system provides a reproducible way to study the adherence of retinal pigment epithelium to normal and diseased human Bruch's membrane.

Aged↗

PubMed1989

Development and characterization of monoclonal antibodies directed against the retinal pigment epithelial cell.

The retinal pigment epithelium consists of a unicellular layer of neuroepithelial cells that are essential for the maintenance of normal function of the neural retina. In order to evaluate more critically this cell in health and disease, we prepared monoclonal antibodies against human retinal pigment epithelial (RPE) cells. Balb/c mice were immunized with human RPE cells. Spleen cells were fused with myeloma cells and resultant hybridomas were selected for antibody production. Supernatants were assayed by immunoperoxidase on frozen sections of human eye tissues. Two hybrids were cloned and ascites were generated in mice. These IgG antibodies react only with RPE cells and show no cross-reactivity with other cells in the eye or with human brain, kidney, skin, salivary glands, lymphocytes or monocytes. These antibodies recognize cell surface molecules that are highly conserved since they can be found in man, monkey, rat, cow, chicken and frog. SDS gel electrophoresis and immunoblot analysis showed that one of the antibodies reacted with a 42,000 MW polypeptide. Evaluation of the developing rat retina revealed that the epitopes are not detected at birth, are weakly present at day 6 and are highly recognized by day 9. These immunoglobulins will allow us to evaluate RPE cells in disease (proliferation, migration) and to probe the bioregulatory functions (phagocytosis, vitamin A transport) of these cells.

Animals↗

PubMed1984

Changes in the distribution of laminin, fibronectin, type IV collagen and heparan sulfate proteoglycan during colony formation by chick retinal pigment epithelial cells in vitro.

Retinal pigment epithelial cells isolated by non-enzymatic means from 8 day old chick embryos were grown as explants on glass coverslips in culture. Retinal pigment epithelial cells grown in this way form colonies in which three zones, each containing cells with distinctly different morphology, pigmentation, adhesion pattern and cytoskeletal organization, can be distinguished (Turksen et al., 1983). Using specific antisera against laminin, fibronectin, type IV collagen, and heparan sulfate proteoglycan, we have found differences in the distribution of these basement membrane components in the three zones of each colony. When cells were stained with laminin, type IV collagen and fibronectin antibodies, extensive filamentous arrays were observed on the substratum side of the cells. In contrast to type IV collagen which was deposited to a similar degree in all three zones of each colony, laminin and fibronectin were most prominent in the central zone in which the packed cuboidal differentiated cells are located. In contrast to the other components, the heparan sulfate proteoglycan appeared to be associated primarily with the cell surface. Our results support the general view that basement membrane components could influence cell shape through an effect on the cytoskeleton, and play a role in the maintenance and expression of the differentiated state. Thus retinal pigment epithelial cells might provide a very useful model system for studying the interactions between the cytoskeleton and extracellular matrices and the biosynthesis of the BM components in epithelial cells.

Animals↗

PubMed1999

Role of interferon regulatory factor-1 and mitogen-activated protein kinase pathways in the induction of nitric oxide synthase-2 in retinal pigmented epithelial cells.

Bovine retinal pigmented epithelial cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Experiments were performed to investigate the involvement of interferon regulatory factor-1 (IRF-1) on NOS-2 induction and its regulation by NOS-2 inhibitors such as pyrrolidine dithiocarbamate (PDTC), an antioxidant, or protein kinase inhibitors. Analysis by transitory transfections showed that LPS, alone or with IFN-gamma, stimulated activity of the murine NOS-2 promoter fragment linked upstream of luciferase and its suppression by PDTC and by the different protein kinase inhibitors, genistein (tyrosine kinase inhibitor), PD98059 (mitogen-actived protein (MAP) kinase kinase inhibitor), and SB 203580 (p38 MAP inhibitor). Using specific antibodies, we have confirmed that extracellular signal-regulated kinases and p38 MAP kinase were activated by LPS and IFN-gamma in retinal pigmented epithelial cells. Analysis by reverse transcriptase-polymerase chain reaction, Western blot, and electrophoretic mobility shift assay demonstrated that IFN-gamma alone or combined with LPS induced an accumulation of IRF-1 mRNA and protein and IRF-1 DNA binding. Transfections assays with the IRF-1 promoter showed an induction of this promoter with IFN-gamma, potentiated by LPS. The decrease of LPS/IFN-gamma-induced IRF-1 promoter activity, IRF-1 synthesis, and IRF-1 activation, by PDTC, genistein, PD98059, and SB 203580, could explained in part the inhibition of the NOS-2 induction by these compounds. Our results demonstrate that IRF-1 is necessary for NOS-2 induction by LPS and IFN-gamma and that its synthesis requires the involvement of a redox-sensitive step, the activation of tyrosine kinases, and extracellular signal-regulated kinases 1/2 and p38 MAP kinases.

Animals↗

PubMed1991

Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured human retinal pigment epithelium cells.

Cultured retinal pigment epithelium cells prepared from post-mortem adult human eyes are shown to contain muscarinic receptors associated with phosphoinositide turnover. Carbachol at a concentration of 100 microM induced a four-fold increase in 3H-inositol phosphates (more than 76% is in the form of 3H-inositol-1-phosphate) accumulation within 45 min in cells prelabelled with 3H-myoinositol and exposed to 5 mM LiCl. The EC50 of carbachol was approx. 70 microM and the saturation concentration was about 1 mM. The carbachol-induced response was blocked by both atropine and pirenzepine, the former being most effective. Pre-exposure of cells to carbachol resulted in desensitization and a drastic reduction in the subsequent carbachol-induced stimulation of 3H-inositol phosphates. The carbachol response could be attenuated by the biologically active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate, and this was nullified by the protein kinase C inhibitor, staurosporine. The biologically inactive phorbol ester, 4 alpha-phorbol 12,13 dideconoate, did not attenuate the carbachol-induced stimulation of 3H-inositol phosphates. Pertussis toxin failed to influence the carbachol receptor-mediated phosphoinositide turnover. These studies provide clear evidence for the occurrence of muscarinic receptors coupled to phosphoinositide hydrolysis on human retinal pigment epithelium cells.

Adult↗

PubMed2003

Chloride currents in acutely isolated Xenopus retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) regulates the ionic composition of the fluid surrounding the photoreceptors by transport mechanisms that utilize Cl- channels. Cl- currents in RPE cells, however, remain incompletely characterized. The purpose of this study was to identify the Cl- currents in acutely isolated Xenopus RPE cells using whole-cell patch clamp. We describe three different Cl- currents. (1) An inwardly rectifying Cl- current, ICl,ir, activates slowly with hyperpolarization (tauact = ~1 s at -80 mV, V1/2= -94 +/- 3 mV), is blocked by Zn2+ (IC50 =185 microM), is stimulated by acid (ICl,ir is 5 times larger at pH 6 than pH 8), and is blocked by DIDS in a voltage-dependent manner. ICl,ir closely resembles cloned ClC-2currents. (2) An outwardly rectifying Cl- current, ICl,Ca, is stimulated by elevated cytosolic free [Ca2+]. With 1 microM free [Ca2+]i in the patch pipette, ICl,Ca activates slowly with depolarization (tauact =325 ms at 100 mV) and deactivates upon hyperpolarization. ICl,Ca is not blocked by 1 mM Zn2+ or 10 microM Gd3+ but is blocked by DIDS. High extracellular [Ca2+] (10 mM) also activates ICl,Ca. (3) A non-rectifying current is activated by elevation of cytoplasmic cAMP with forskolin and IBMX. In addition to these three Cl- currents, Xenopus RPE cells exhibit a non-selective background current (Ibkg) which has a linear I-V relationship and is voltage insensitive. This current is blocked by Zn2+ (IC50 of 5.3 microM) or 10 microM Gd3+. This description provides new insights into the physiology of Cl- channels involved in salt and fluid transport by the retinal pigment epithelium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2006

Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus).

BACKGROUND: In bluegill sunfish, the melanin-containing pigment granules of the retinal pigment epithelium undergo cyclic movements in response both to ambient lighting and circadian cues. Pigment granules aggregate into the cell body at night (in the dark), and disperse into apical processes during the day (in the light). Regulation of pigment granule aggregation in a number of fishes depends on modulating the intracellular levels of cyclic adenosine monophosphate. RESULTS: Here we show isolated RPE takes up cyclic adenosine monophosphate (cAMP) in a saturable manner, exogenously applied cAMP induces pigment granule aggregation in retinal pigment epithelium isolated from bluegill, and aggregation induced in this manner is inhibited by treatment with probenecid, an organic anion transport inhibitor. CONCLUSION: Our results raise the possibility that cAMP functions as a messenger secreted from the neural retina to signal darkness to the RPE, which takes it up. It further suggests that organic anion transport systems are the route by which cAMP crosses RPE cell membranes since probenecid inhibits extracellular cAMP from causing pigment granule aggregation.

Animals↗

PubMed2006

Pigment epithelium-derived factor protects retinal pigment epithelium from oxidant-mediated barrier dysfunction.

Retinal pigment epithelium (RPE) cells form a monolayer at the blood-retina barrier between the retina and choriocapillaries. The barrier function may be damaged by multiple stresses to the cell, including the repeated exposure to oxidants that are generated by photoreceptor cell turnover. The purpose of our study was to document the protective effect of pigment epithelium-derived factor (PEDF), a tropic factor produced by the RPE, on H(2)O(2)-induced RPE barrier dysfunction. When assayed by a FITC-labeled dextran transepithelial flux, the increased permeability of the RPE barrier (induced by H(2)O(2)) was prevented by PEDF pretreatment. To further explore the mechanism leading to this permeability change, we investigated the distribution of cytoskeleton and junctional proteins. The redistribution of the two junctional proteins occludin, and N-cadherin and actin reorganization in RPE, induced by H(2)O(2), can be prevented by PEDF pretreatment. PEDF can also prevent H(2)O(2)-induced stress kinase p38/27-kDa heat shock protein signaling which is known to mediate actin rearrangement. These findings indicated that PEDF can stabilize actin, maintain normal membrane occludin and N-cadherin structure, and preserve the barrier function of RPE cells against oxidative stress.

Actins↗

PubMedDate not supplied

Indocyanine green angiography pattern of congenital grouped albinotic retinal pigment epithelial spots.

Congenital grouped albinotic retinal pigment epithelial spots (CGARPES) is a rare retinal pigment epithelium disease with multiple, white spots, generally involving the peripheral retina, with variable angiographic pattern. A 46-year-old male affected by CGARPES underwent fluorescein angiography and indocyanine green videoangiography. Fluorescein angiography demonstrated an early hyperfluorescence of the spots. A peculiar pattern was revealed by indocyanine green videoangiography. Indeed, during the early phases the spots were either not detectable on the choroidal background, or presented slightly hypofluorescent, whereas during the intermediate and the late phases some spots became progressively hyperfluorecent. The angiographic behavior on indocyanine green may be explained considering a gradual staining of the lesions, with a progressive binding between the indocyanine green molecule and the abnormal retinal pigment epithelium material.

Albinism, Ocular↗

PubMed1998

Photosensitization of retinal pigment epithelium by protoporphyrin IX.

BACKGROUND: Clinical evidence of injury to the retinal pigment epithelium is an important feature of age-related macular degeneration, but the mechanism of this injury is unknown. Blue-light-dependent activation of the blood-borne photosensitizer protoporphyrin IX is known to produce free radicals which may damage cells and tissues. This study was undertaken to determine the effect of blue light and protoporphyrin IX on retinal pigment epithelial cells in vitro. METHODS: Third-passage porcine retinal pigment epithelial cells were plated in six-well culture plates at 100,000 cells/well and grown to confluence. Retinal pigment epithelial cells were then incubated in culture media with and without 35 micrograms/dl protoporphyrin IX and exposed to low intensity (118 microW/cm2) blue, blue-free, or full-spectrum white light in an irradiating incubator for 16 h on/8 h off cycles for 7 days. Some of the wells were shielded from light (dark controls). Retinal pigment epithelial cells were examined by light microscopy and were trypsinized and counted after 7 days. RESULTS: White light with and without protoporphyrin IX and protoporphyrin IX in dark conditions did not decrease the retinal pigment epithelial cell count significantly. Blue light alone and blue light with protoporphyrin IX decreased the cell count by 22 +/- 4% and 35 +/- 3% compared to the controls, respectively. CONCLUSION: Blue wavelength light without exogenous protoporphyrin IX has a cytotoxic effect on confluent cultures of retinal pigment epithelium, suggesting that endogenous photosensitizers may be present in retinal pigment epithelial cells. Protoporphyrin IX has an additive cytotoxic effect in the presence of blue light, suggesting that this photosensitizer is capable of mediating blue-light-induced retinal pigment epithelial damage. Since protoporphyrin IX is present in blood and tissue fluids, and the retina is chronically exposed to light, protoporphyrin IX-mediated free radical formation may occur in vivo and may play a role in retinal pigment epithelial changes that occur early in the pathogenesis of age-related macular degeneration.

Animals↗

PubMed1999

Retinal pigment epithelial dysfunction in human immunodeficiency virus-infected patients with cytomegalovirus retinitis.

OBJECTIVE: Prior clinical observations led the authors to examine electrophysiologic measures of retinal (electroretinogram [ERG]) and retinal pigment epithelial (electro-oculogram [EOG]) function in patients infected with human immunodeficiency virus (HIV) who either had or did not have cytomegalovirus (CMV) retinitis in order to determine if the ERG or EOG measures were differentially affected in CMV retinitis. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-one HIV-infected patients (20 with and 21 without CMV retinopathy) were evaluated. INTERVENTION: ERGs and EOGs were recorded. Patients' fundi were evaluated by indirect ophthalmoscopy or fundus photography. MAIN OUTCOME MEASURES: The ERG a- and b-wave amplitudes and EOG light/dark amplitude ratio (L/D ratio) from the eyes of all patients were compared with values 2 standard deviations from the mean of a normal sample. The area of the retinal lesions was estimated from fundus photographs or from careful drawings made during indirect ophthalmoscopy. RESULTS: The majority of the eyes (64.5%) of the patients with CMV retinitis had subnormal L/D ratios, and most eyes (95%) of patients without CMV retinitis had normal L/D ratios. Only six eyes (four with and two without CMV retinopathy) had subnormal a-wave amplitudes, and there was no significant correlation between a-wave amplitude and the L/D ratio for patients with CMV retinitis. Most eyes (80.6%) of the patients with CMV retinitis had subnormal b-wave amplitudes, but there was no significant correlation between b-wave amplitude and L/D ratio in the patients with CMV retinitis. In three patients with CMV retinitis selected to exemplify the range of effects on the ERG and EOG, the b-wave amplitude loss was roughly proportional to the area of retina visibly affected in indirect ophthalmoscopy. One patient had a nonrhegmatogenous retinal detachment. CONCLUSIONS: Middle retinal function, as reflected in the b-wave amplitude, and retinal pigment epithelial function, as reflected in the L/D ratio, were both compromised in CMV retinitis, but the effect on function in the two layers of the retina appeared independent because there was no significant correlation between the L/D ratio and b-wave amplitude. The decrease in L/D ratio was not secondary to loss of photoreceptor function and probably represents a dysfunction of the retinal pigment epithelium because there was no significant correlation between a-wave amplitude, which was normal in most cases, and L/D ratio. The inner retinal pathology of CMV retinitis is visible clinically and was associated with decreases in b-wave amplitude in this and previous studies. The significant independent retinal pigment epithelial dysfunction demonstrated in this study may be an important predisposing factor to retinal detachment in CMV retinitis.

AIDS-Related Opportunistic Infections↗