TRPV4 and chloride channels mediate volume sensing in trabecular meshwork cells

Author:

Baumann Jackson M.12,Yarishkin Oleg1ORCID,Lakk Monika1,De Ieso Michael L.3,Rudzitis Christopher N.4,Kuhn Megan3,Tseng Yun Ting1,Stamer W. Daniel3ORCID,Križaj David124ORCID

Affiliation:

1. Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, Utah, United States

2. Department of Bioengineering, University of Utah School of Medicine, Salt Lake City, Utah, United States

3. Duke Eye Center, Duke University, Durham, North Carolina, United States

4. Department of Neurobiology, University of Utah, Salt Lake City, Utah, United States

Abstract

Intraocular pressure is dynamically regulated by the flow of aqueous humor through paracellular passages within the trabecular meshwork (TM). This study shows hypotonic gradients that expand the TM cell volume and reduce the outflow facility in mouse eyes. The swelling-induced current consists of TRPV4 and chloride components, with TRPV4 as a driver of swelling-induced calcium signaling. TRPV4 inhibition reduced swelling, suggesting a novel treatment for trabeculitis and glaucoma.

Funder

Crandall Glaucoma Initiative

HHS | NIH | National Eye Institute

Research to Prevent Blindness

Publisher

American Physiological Society

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