The retinal pigment epithelium (RPE) is a monolayer of cells separating the neurosensory retina and the choroidal blood supply which performs a wide range of functions that are necessary to health of the retina. The transport of ions by these epithelial cells is critical to the visual process because it regulates the environment of the photoreceptors and because it helps maintain retinal adhesion. The long term objective of the work proposed here is to provide a detailed description of the mechanisms and regulation of this ion transport. Like other transporting epithelia, the RPE has an asymmetric distribution of ion pumps and conductances in its two membranes which make up cellular transport systems that mediate the transcellular movement of ions. Recently developed methods allow a detailed study of these conductances in single, isolated RPE cells. The immediate aims are: (1) to identify in single cells specific conductances that are thought to be the basis for transcellular ion transport; (2) to localize these conductances to the apical or the basolateral membrane; (3) to examine the regulation of specific conductances, especially with regard to modulation by cyclic AMP; and (4) to identify and characterize the single channels that are the molecular basis for the conductances.
These aims will be pursued using the patch-clamp technique to record macroscopic and single-channel currents in intact RPE cells and in membrane fragments. It is expected that these studies will result in a better understanding of how individual transport molecules are regulated so as maintain normal transport function in the RPE.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences A Study Section (VISA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Zhang, Xiaoming; Hughes, Bret A (2013) KCNQ and KCNE potassium channel subunit expression in bovine retinal pigment epithelium. Exp Eye Res 116:424-32
Zhang, Wei; Zhang, Xiaoming; Wang, Hui et al. (2013) Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy. Am J Physiol Cell Physiol 304:C440-9
Pattnaik, Bikash R; Hughes, Bret A (2012) Effects of KCNQ channel modulators on the M-type potassium current in primate retinal pigment epithelium. Am J Physiol Cell Physiol 302:C821-33
Zhang, Xiaoming; Yang, Dongli; Hughes, Bret A (2011) KCNQ5/K(v)7.5 potassium channel expression and subcellular localization in primate retinal pigment epithelium and neural retina. Am J Physiol Cell Physiol 301:C1017-26
Yang, Dongli; Elner, Susan G; Clark, Andrea J et al. (2011) Activation of P2X receptors induces apoptosis in human retinal pigment epithelium. Invest Ophthalmol Vis Sci 52:1522-30
Pattnaik, Bikash R; Hughes, Bret A (2009) Regulation of Kir channels in bovine retinal pigment epithelial cells by phosphatidylinositol 4,5-bisphosphate. Am J Physiol Cell Physiol 297:C1001-11
Yang, Dongli; Zhang, Xiaoming; Hughes, Bret A (2008) Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium. Exp Eye Res 87:176-83
Yang, Dongli; Swaminathan, Anuradha; Zhang, Xiaoming et al. (2008) Expression of Kir7.1 and a novel Kir7.1 splice variant in native human retinal pigment epithelium. Exp Eye Res 86:81-91
Hughes, Bret A; Swaminathan, Anuradha (2008) Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH. Am J Physiol Cell Physiol 294:C423-31
Kindzelskii, Andrei L; Elner, Victor M; Elner, Susan G et al. (2004) Human, but not bovine, photoreceptor outer segments prime human retinal pigment epithelial cells for metabolic activation and massive oxidant release in response to lipopolysaccharide and interferon-gamma. Exp Eye Res 79:431-5

Showing the most recent 10 out of 26 publications