Vacuolar H+-ATPase in ocular ciliary epithelium

Martin B. Wax, Isao Saito, Tatyana Tenkova, Theodore Krupin, Bernard Becker, Nathan Nelson, Dennis Brown, Stephen L. Gluck

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Abstract

The mechanisms controlling the production of aqueous humor and the regulation of intraocular pressure are poorly understood. Here, we provide evidence that a vacuolar H+-ATPase (V-ATPase) in the ocular ciliary epithelium is a key component of this process. In intracellular pH (pH(i)) measurements of isolated ciliary epithelium performed with 2',7- biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), the selective V-ATPase inhibitor bafilomycin A1 slowed the recovery of pH(i) in response to acute intracellular acidification, demonstrating the presence of V-ATPase in the plasma membrane. In isolated rabbit ciliary body preparations examined under voltage-clamped conditions, bafilomycin A1 produced a concentration- dependent decrease in short-circuit current, and topical application of bafilomycin A1 reduced intruocular pressure in rabbits, indicating an essential role of the V-ATPase in ciliary epithelial ion transport. Immunocytochemistry utilizing antibodies specific for the B1 isoform of the V-ATPase 56-kDa subunit revealed localization of V-ATPase in both the plasma membrane and cytoplasm of the native ciliary epithelium in both rabbit and rat eye. The regional and subcellular distribution of V-ATPase in specific regions of the ciliary process was altered profoundly by isoproterenol and phorbol esters, suggesting that change in the intracellular distribution of the enzyme is a mechanism by which drugs, hormones, and neurotransmitters modify aqueous humor production.

Original languageEnglish (US)
Pages (from-to)6752-6757
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number13
DOIs
StatePublished - Jun 24 1997

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Wax, M. B., Saito, I., Tenkova, T., Krupin, T., Becker, B., Nelson, N., Brown, D., & Gluck, S. L. (1997). Vacuolar H+-ATPase in ocular ciliary epithelium. Proceedings of the National Academy of Sciences of the United States of America, 94(13), 6752-6757. https://doi.org/10.1073/pnas.94.13.6752