Effect of Valproic Acid on Nitric Oxide and Nitric Oxide Synthase in Trabecular Meshwork Cell

ABSTRACT

PURPOSE: To investigate the effects of valproic acid on the production of nitric oxide (NO) and expression of endothelial nitric oxide synthase (eNOS) in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0.25, 0.5, and 1.0 mM valproic acid for 6, 12, and 24 hours. Expression of eNOS mRNA was assessed with Reverse transcription-polymerase chain reaction, and production of NO was assessed with Griess assay. Cellular survival was assessed with the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Valproic acid at concentrations of 0.25, 0.5, 1.0 mM did not affect the cellular survival of HTMC significantly after exposure for 24 hours. Valproic acid increased NO production in a dose- and time-dependent manner. Also, valproic acid increased the degree of eNOS mRNA expression in a dose-dependent manner in HTMC. CONCLUSIONS: Valproic acid increases production of NO and expression of eNOS mRNA in HTMC. Thus, valproic acid might increase aqueous outflow through the trabecular meshwork.