TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure.

Sappington RM, Sidorova T, Long DJ, Calkins DJ
Invest Ophthalmol Vis Sci. 2009 50 (2): 717-28

PMID: 18952924 · PMCID: PMC3549616 · DOI:10.1167/iovs.08-2321

PURPOSE - Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to pressure sensing and Ca(2+)-dependent cell death in other systems, also contributes to pressure-induced RGC death and whether this contribution involves Ca(2+).

METHODS - trpv1 mRNA expression in RGCs was probed with the use of PCR and TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin) and agonism (capsaicin) were used to probe how TRPV1 activation affects the survival of isolated RGCs at ambient and elevated hydrostatic pressure (+70 mm Hg). Finally, for RGCs under pressure, the authors tested whether EGTA chelation of Ca(2+) improves survival and whether, with the Ca(2+) dye Fluo-4 AM, TRPV1 contributes to increased intracellular Ca(2+).

RESULTS - RGCs express trpv1 mRNA, with robust TRPV1 protein localization to the cell body and axon. For isolated RGCs under pressure, TRPV1 antagonism increased cell density and reduced apoptosis to ambient levels (P
CONCLUSIONS - RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca(2+).

MeSH Terms (19)

Animals Apoptosis Axons Blotting, Western Calcium Diterpenes Hydrostatic Pressure In Situ Hybridization Intraocular Pressure Mice Mice, Inbred C57BL Mice, Inbred DBA Microscopy, Fluorescence Rats Rats, Sprague-Dawley Retinal Ganglion Cells Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger TRPV Cation Channels

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