The overall goal for this project is to forge a series of links between transepithelial transport processes and the individual membrane mechanisms (apical and/or basolateral) that help regulate the chemical composition of the intracellular milieu. In order to study this relationship we will use tracer flux techniques to determine the magnitude and direction of active ion transport across the pigment epithelium (PE). We will use conventional and ion-selective microelectrodes to determine the driving forces for passive and active (or carrier mediated) transport processes. Fluid transport will also be measured and we will determine which active transport mechanisms are osmotically coupled to fluid flow. Fluorescence techniques will be used to measure intracellular pH and Ca. One of the important goals of this project is to test the fundamental hypothesis that mechanisms which play an important role in regulating intracellular pH and Ca also regulate transepithelial ion and fluid transport and the chemical milieu of the subretinal and choroidal spaces. The electrooculogram (EOG) is a light evoked change in standing potential across the human eye and is produced by a depolarization of the RPE basolateral membrane. The clinical evaluation of PE disease might be improved if we knew which membrane mechanisms were responsible for the EOG light peak. Similarly, we could gain a much deeper understanding of retinal detachments if we know which membrane mechanisms are responsible for fluid transport across the RPE. It will be important to examine the adhesivity between pigment epithelium and retina as a function of PE fluid transport rate. If intracellular pH regulation played a key role in phagocytosis and disc shedding, or in controlling the esteryfing enzymes in the vitamin A cycle, it could be important for understanding RPE pathogenesis.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences A Study Section (VISA)
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University of California Berkeley
Schools of Optometry/Opht Tech
United States
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Voloboueva, Ludmila A; Killilea, David W; Atamna, Hani et al. (2007) N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration. FASEB J 21:4077-86
Voloboueva, Ludmila A; Liu, Jiankang; Suh, Jung H et al. (2005) (R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage. Invest Ophthalmol Vis Sci 46:4302-10
Liou, Gregory I; Samuel, Sara; Matragoon, Suraporn et al. (2004) Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium. Mol Vis 10:383-91
Wang, Fei; Rendahl, Katherine G; Manning, William C et al. (2003) AAV-mediated expression of vascular endothelial growth factor induces choroidal neovascularization in rat. Invest Ophthalmol Vis Sci 44:781-90
Maminishkis, Arvydas; Jalickee, Stephen; Blaug, Sasha A et al. (2002) The P2Y(2) receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat. Invest Ophthalmol Vis Sci 43:3555-66
Quinn, R H; Quong, J N; Miller, S S (2001) Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium. Invest Ophthalmol Vis Sci 42:255-64
Rymer, J; Miller, S S; Edelman, J L (2001) Epinephrine-induced increases in [Ca2+](in) and KCl-coupled fluid absorption in bovine RPE. Invest Ophthalmol Vis Sci 42:1921-9
Uyekubo, S N; Fischer, H; Maminishkis, A et al. (1998) cAMP-dependent absorption of chloride across airway epithelium. Am J Physiol 275:L1219-27
Kenyon, E; Maminishkis, A; Joseph, D P et al. (1997) Apical and basolateral membrane mechanisms that regulate pHi in bovine retinal pigment epithelium. Am J Physiol 273:C456-72
Peterson, W M; Meggyesy, C; Yu, K et al. (1997) Extracellular ATP activates calcium signaling, ion, and fluid transport in retinal pigment epithelium. J Neurosci 17:2324-37

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