(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one alleviates lipoteichoic acid-induced photoreceptor cell damage

Exposure to oxidative stress will lead to the progression of retinal degenerative diseases, and unfortunately the exact mechanisms have not been fully understood. In this study, the protective effects of (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) against the lipoteichoic acid (LTA)-induced cell damage in mouse photoreceptor-derived 661W cells were investigated.661W cells were pre-treated with TIM at different concentrations (0.1-2.5 μM) before exposure to LTA. The oxidative stress and inflammatory response were detected in 661W cells.Pre-treatment of 661W cells with TIM (0.1-2.5 μM) for 4 h significantly decreased the LTA-induced toxicity. Meanwhile, pre-treatment with TIM could attenuate the imbalance state of redox in 661W cells by decreasing the levels of intracellular ROS and MDA, as well as enhancing the SOD activity and the level of GSH, through increasing the protein expression of Nrf2. Moreover, TIM pre-treatment decreased pro-inflammatory factors IL-1β, IL-12 and TNFα, through inhibiting the nuclear factor kappa B. Pre-treatment with TIM also suppressed Egr1, Fosl1, and Lox12 gene expression.These results suggested that TIM may exert its protective effects against LTA-induced toxicity in 661W cells, through counteracting the oxidative stress and inhibiting inflammatory response. Our findings provided the scientific rational to develop TIM in the treatment of oxidative stress-induced photoreceptor cell damage.