Abstract:AIM: To investigate the modulator action of resveratrol (RSV) through the suppression of transient receptor potential ankyrin 1 (TRPA1) on the hypoxia (HPO)-caused oxidative degeneration and apoptosis in human retinal pigment epithelial cells (ARPE19). METHODS: The control (CNT), RSV (50 µmol/L for 24h), HPO (200 µmol/L CoCl2 for 24h), and HPO+RSV groups were induced in the ARPE19. Apoptosis, caspases (caspases 3, 8, and 9), oxidants [lipid peroxidation, oxygen free radical (OFR), and dysfunction of mitochondrial membrane], antioxidants (glutathione and glutathione peroxidase), Ca2+, Zn2+ levels, live cell number and percentage were all measured in the cells of four groups. RESULTS: The HPO increased Ca2+ and Zn2+ fluorescence intensity in the cells. It also upregulated the apoptosis, caspases, and oxidant indicators while downregulating the antioxidants, and the count of live cells. TRPA1 agonist (cinnamonaldehyde) further upregulated these indicators (all P<0.05). When the HPO-induced increase in TRPA1 activation was treated with RSV and the TRPA1 antagonist (AP18), cell viability and antioxidants rose while the oxidant and apoptotic indicators decreased due to TRPA1 suppression (P<0.05). CONCLUSION: HPO exposure through TRPA1-mediated Ca2+ signaling, induces mitochondrial oxidative cell cytotoxicity and death, which may offer a treatment option for HPO-induced retinal disorders linked to increased OFR and Ca2+ influx.
