1α,25-dihydroxyvitamin D3 attenuates oxidative stress-induced damage in human trabecular meshwork cells by inhibiting TGFß-SMAD3-VDR pathway.

Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)2D3 in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) and showed that 1, 25-(OH)2D3 could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)2D3 could attenuate H2O2-induced inflammation in HTMCs. Mechanistically, our findings revealed that H2O2-induced damage was mediated by the transforming growth factor-ß (TGF-ß)-SMAD3 pathway in HTMCs, and 1, 25-(OH)2D3 could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)2D3 reduces ECM accumulation and suppresses the TGF-ß-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)2D3 might be a potential therapeutic for glaucoma.