Potassium-evoked responses from the retinal pigment epithelium of the toad Bufo marinus

Mutations in genes expressed in the retinal pigment epithelium (RPE) underlie a number of human inherited retinal disorders that manifest with photoreceptor degeneration. Because light-evoked responses of the RPE are generated secondary to rod photoreceptor activity, RPE response reductions observed in human patients or animal models may simply reflect decreased photoreceptor input. The purpose of this study was to define how the electrophysiological characteristics of the RPE change when the complement of rod photoreceptors is decreased. To measure RPE function, we used an electroretinogram (dc-ERG)-based technique. We studied a slowly progressive mouse model of photoreceptor degeneration ( Prph Rd2/+), which was crossed onto a Nyxnob background to eliminate the b-wave and most other postreceptoral ERG components. On this background, Prph Rd2/+ mice display characteristic reductions in a-wave amplitude, which parallel those in slow PIII amplitude and the loss of rod photoreceptors. At 2 and 4 mo of age, the amplitude of each dc-ERG component (c-wave, fast oscillation, light peak, and off response) was larger in Prph Rd2/+ mice than predicted by rod photoreceptor activity (RmP3) or anatomical analysis. At 4 mo of age, the RPE in Prph Rd2/+ mice showed several structural abnormalities including vacuoles and swollen, hypertrophic cells. These data demonstrate that insights into RPE function can be gained despite a loss of photoreceptors and structural changes in RPE cells and, moreover, that RPE function can be evaluated in a broader range of mouse models of human retinal disease.

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Potential, Current, and Ionic Fluxes across the Isolated Retinal Pigment Epithelium and Choroid

The Journal of General Physiology ◽

10.1085/jgp.49.5.913 ◽

1966 ◽

Vol 49 (5) ◽

pp. 913-924 ◽

Cited By ~ 59

Author(s):

Arnaldo Lasansky ◽

Felisa W. de Fisch

Keyword(s):

Retinal Pigment Epithelium ◽

Short Circuit ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Short Circuit Current ◽

Bufo Marinus ◽

Flux Chamber ◽

Epithelial Surface ◽

The Mean

A flux chamber was utilized for in vitro studies of a membrane formed by the retinal pigment epithelium and choroid of the eye of the toad (Bufo arenarum and Bufo marinus). A transmembrane potential of 20 to 30 mv was found, the pigment epithelium surface positive with respect to the choroidal surface. Unidirectional fluxes of chloride, sodium, potassium, and calcium were determined in the absence of an electrochemical potential difference. A net transfer of chloride from pigment epithelium to choroid accounted for a major fraction of the mean short-circuit current. A small net flux of sodium from choroid to pigment epithelium was detected in Bufo marinus. In both species of toads, however, about one-third of the mean short-circuit current remained unaccounted for. Manometric determinations of bicarbonate suggested an uptake of this ion at the epithelial surface of the membrane but did not provide evidence of a relationship between this process and the short-circuit current.

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Ba2+ unmasks K+ modulation of the Na+-K+ pump in the frog retinal pigment epithelium.

The Journal of General Physiology ◽

10.1085/jgp.86.6.853 ◽

1985 ◽

Vol 86 (6) ◽

pp. 853-876 ◽

Cited By ~ 32

Author(s):

E R Griff ◽

Y Shirao ◽

R H Steinberg

Keyword(s):

Retinal Pigment Epithelium ◽

Channel Blocker ◽

Apical Membrane ◽

Pigment Epithelium ◽

Retinal Pigment ◽

K Channel ◽

Evoked Responses ◽

Physiological Conditions ◽

Transepithelial Potential ◽

Slow Piii

This paper presents electrophysiological evidence that small changes in [K+]o modulate the activity of the Na+-K+ pump on the apical membrane of the frog retinal pigment epithelium (RPE). This membrane also has a large relative K+ conductance so that lowering [K+]o hyperpolarizes it and therefore increases the transepithelial potential (TEP). Ba2+, a K+ channel blocker, eliminated these normal K+-evoked responses; in their place, lowering [K+]o evoked an apical depolarization and TEP decrease that were blocked by apical ouabain or strophanthidin. These data indicate that Ba2+ blocked the major K+ conductance(s) of the RPE apical membrane and unmasked a slowing of the normally hyperpolarizing electrogenic Na+-K+ pump caused by lowering [K+]o. Evidence is also presented that [K+]o modulates the pump in the isolated RPE under physiological conditions (i.e., without Ba2+). In the intact retina, light decreases subretinal [K+]o and produces the vitreal-positive c-wave of the electroretinogram (ERG) that originates primarily in the RPE from a hyperpolarization of the apical membrane and TEP increase. When Ba2+ was present in the retinal perfusate, the apical membrane depolarized in response to light and the TEP decreased so that the ERG c-wave inverted. The retinal component of the c-wave, slow PIII, was abolished by Ba2+. The effects of Ba2+ were completely reversible. We conclude that Ba2+ unmasks a slowing of the RPE Na+-K+ pump by the light-evoked decrease in [K+]o. Such a response would reduce the amplitude of the normal ERG c-wave.

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Three light-evoked responses of the retinal pigment epithelium

Vision Research ◽

10.1016/0042-6989(83)90107-4 ◽

1983 ◽

Vol 23 (11) ◽

pp. 1315-1323 ◽

Cited By ~ 50

Author(s):

Roy H. Steinberg ◽

Robert A. Linsenmeier ◽

Edwin R. Griff

Keyword(s):

Retinal Pigment Epithelium ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Evoked Responses

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Light-Evoked Responses of the Mouse Retinal Pigment Epithelium

Journal of Neurophysiology ◽

10.1152/jn.00958.2003 ◽

2004 ◽

Vol 91 (3) ◽

pp. 1134-1142 ◽

Cited By ~ 43

Author(s):

Jiang Wu ◽

Neal S. Peachey ◽

Alan D. Marmorstein

Keyword(s):

Retinal Pigment Epithelium ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Inbred Strains ◽

Experimental Manipulation ◽

Mutant Mice ◽

Rod Photoreceptor ◽

Evoked Responses ◽

Stimulus Response ◽

Mouse Mutants

In response to light, the retinal pigment epithelium (RPE) generates a series of slow potentials that can be recorded as the c-wave, fast oscillation (FO), and light peak (LP) of the electroretinogram (ERG). As these potentials can be related to specific cellular events, they provide information about RPE function and how that may be altered by disease or experimental manipulation. In the present study we describe a noninvasive means for recording the light-evoked responses of the mouse RPE and use this to define the stimulus-response properties of the major components in three inbred strains of mice (BALBc/ByJ, C57BL/6J, and 129/SvJ) and two mouse mutants that reduce activity in the rod pathway. All of the major ERG components generated by the RPE are readily measured in the mouse. In albino strains (BALBc/ByJ and 129/SvJ) the intensity-response functions for the c-wave, FO, and LP are shifted toward lower intensities in comparison to those for C57BL/6J mice. Each of these components was markedly reduced in mice lacking transducin in which rod phototransduction is interrupted, indicating that they reflect primarily rod photoreceptor activity. All components were observed in no b-wave ( nob) mutant mice, indicating that inner retinal activity does not make a major contribution to these potentials. Further studies of mutant mice will allow us to define the functional consequences of gene manipulation on RPE function and to evaluate specific hypotheses regarding the generation of ERG components.

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Effects of adenosine on chick retinal pigment epithelium: Membrane potentials and light-evoked responses

Current Eye Research ◽

10.3109/02713689508998496 ◽

1995 ◽

Vol 14 (8) ◽

pp. 685-691 ◽

Cited By ~ 9

Author(s):

Futoshi Maruiwa ◽

Nobuhisa Nao-i ◽

Syuji Nakazaki ◽

Atsushi Sawada

Keyword(s):

Retinal Pigment Epithelium ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Membrane Potentials ◽

Evoked Responses

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Effects of melatonin on the chick retinal pigment epithelium: Membrane potentials and light-evoked responses

Experimental Eye Research ◽

10.1016/s0014-4835(89)80056-9 ◽

1989 ◽

Vol 49 (4) ◽

pp. 573-589 ◽

Cited By ~ 25

Author(s):

Nobuhisa Nao-I ◽

Seven Erik G. Nilsson ◽

Ron P. Gallemore ◽

Roy H. Steinberg

Keyword(s):

Retinal Pigment Epithelium ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Membrane Potentials ◽

Evoked Responses

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High-voltage electron microscopy of subretinal scar formation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122836 ◽

1992 ◽

Vol 50 (1) ◽

pp. 486-487

Author(s):

G.E. Korte ◽

M. Marko ◽

G. Hageman

Keyword(s):

Electron Microscopy ◽

Monoclonal Antibody ◽

Retinal Pigment Epithelium ◽

Glial Cells ◽

High Voltage ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Sodium Iodate ◽

High Voltage Electron Microscopy ◽

Voltage Electron

Sodium iodate iv. damages the retinal pigment epithelium (RPE) in rabbits. Where RPE does not regenerate (e.g., 1,2) Muller glial cells (MC) forma subretinal scar that replaces RPE. The MC response was studied by HVEM in 3D computer reconstructions of serial thick sections, made using the STEREC0N program (3), and the HVEM at the NYS Dept. of Health in Albany, NY. Tissue was processed for HVEM or immunofluorescence localization of a monoclonal antibody recognizing MG microvilli (4).

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