Our overall objectives are to understand the mechanism(s) by which the pigment epithelium (RPE) supports the function of the neural retina. The emphasis will be on RPE-photoreceptor interactions that occur across the subretinal space, through changes in concentrations of substances that follow absorption of light by photoreceptors. Principal objectives are: (1) to understand the mechanism of the RPE basal membrane depolarization (light-peak); (2) to explore effects of mild hypoxia on RPE-photoreceptor interactions and determine if effects occur on retinal processing at threshold scotopic levels; (3) to describe changes in retinal pH and (Ca2+)o that may affect RPE function and that inform about photoreceptor metabolism in the dark, during illumination and when altered by hypoxia; (4) to describe and analyze membrane and single channel currents from isolated RPE cells. Experiments will be performed on the intact cat eye (F. Domesticus), on in vitro preps. of isolated retina-RPE-choroid and RPE-choroid from chicks (G. Domesticus) and on isolated RPE cells from frogs (R. Catesbeiana, R. Pipiens) and chicks. Techniques consist of extracellular and intracellular voltage recording, ion-selective microelectrodes (K+, Ca2+ and H+) and patch micropipettes. For the light peak we hypothesize a change in concentration in the subretinal space of a first messenger from photoreceptors, that through a second messenger in the RPE (? CAMP), alters anion (? C1-) flux across the basolateral RPE membrane. Pharmacological strategies will be used to pursue the first and second messengers. Patch-clamp studies will identify and characterize ionic currents separately from apical and basal membranes and their responses to first and second messengers. We will describe how (H+)o and (Ca+)o in the subretinal space are affected by light and dark, carbonic-anhydrase inbibition (H+) and by mild systemic hypoxia. The hypotheses are that: (1) light reduces Na+-K+ pump activity, thereby decreasing acid production and subretinal (H+) at the inner segment; (2) mild hypoxia also reduces Na+-K pump rate and will alter (H+) and perhaps (Ca2+); (3) mild hypoxia may affect retinal processing at threshold scotopic levels. The studies should contribute to knowledge of mechanisms by which the RPE supports the photoreceptors and the affect of pathophysiological events. They should also inform about the origin of the light peak, which is used to follow RPE and neural retinal disease in humans.

National Institute of Health (NIH)
National Eye Institute (NEI)
Method to Extend Research in Time (MERIT) Award (R37)
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Visual Sciences A Study Section (VISA)
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Cao, W; Li, F; Steinberg, R H et al. (2001) Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina. Exp Eye Res 72:591-604
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Cao, W; Wen, R; Li, F et al. (1997) Mechanical injury increases bFGF and CNTF mRNA expression in the mouse retina. Exp Eye Res 65:241-8
Cao, W; Wen, R; Li, F et al. (1997) Induction of basic fibroblast growth factor mRNA by basic fibroblast growth factor in Muller cells. Invest Ophthalmol Vis Sci 38:1358-66
LaVail, M M; Matthes, M T; Yasumura, D et al. (1997) Variability in rate of cone degeneration in the retinal degeneration (rd/rd) mouse. Exp Eye Res 65:45-50

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