Angiotensin II type 1 receptor blockade suppresses H₂O₂-induced retinal degeneration in photoreceptor cells

Abstract

Exposure to reactive oxygen species (ROS) leads to the development and progression of retinal degenerative diseases. However, the exact mechanisms are not fully understood. In this article, the role of angiotensin II type 1 receptor (AT1R) signaling in H₂O₂-induced retinal damage was examined. Mouse photoreceptor-derived 661 W cells were treated with the AT1R blockers valsartan, losartan and candesartan before exposure to H₂O₂. Cell viability, intracellular ROS level, mitochondrial membrane potential (MMP), cytochrome-c level, DNA fragmentation, caspase activity and gene expression were detected. Pre-treatment of 661 W cells with AT1R blockers significantly decreased H₂O₂-mediated toxicity and reduced the ROS level. In addition, apoptosis-related biochemical indicators showed that pre-incubation of AT1R blockers would elevate the MMP, decrease the release of cytochrome-c and formation of DNA fragmentation, and inhibit activities of caspase-3 and caspase-9 in exogenous H₂O₂-treated 661 W cells. Moreover, treatment with AT1R blockers suppressed the expression of Egr1, Fosl1 and Lox12. These results suggest that AT1R signaling mediates H₂O₂-induced apoptosis, at least partially through generating the ROS and increasing the levels of proapoptotic molecules in 661 W cells. AT1R blockade may provide a new therapeutic approach for preventing oxidative stress-induced retinal neural damage.

• 661 W cell
• apoptosis
• AT1R blockers
• H₂O₂
• oxidative stress
• retina

Declaration of interest

All authors declare that there are no conflicts of interest concerning this article.