Lactate protects against oxidative stress-induced retinal degeneration by activating autophagy.

Age-related macular degeneration is a common cause of blindless among the aged, which can mainly be attributed to oxidative stress and dysregulated autophagy in retinal pigment epithelium cells. Lactate was reported to act as a signaling molecule and exerted beneficial effect against oxidative stress. This study aims to investigate the protective effect of lactate against oxidative stress-induced retinal degeneration. Here, H ₂ O ₂ -induced oxidative stress cell model and sodium iodate-induced mice retinal degeneration model were established. It was found that H ₂ O ₂ inhibited cell viability in ARPE-19 cells and sodium iodate induced deterioration of retinal pigment epithelium as well as apoptosis in retina. Pretreatment with lactate alleviated oxidative stress-induced cell death and retinal degeneration. Molecularly, lactate activated autophagy by up-regulating the ratio of LC3II/I, increased formation of LC3 puncta and autophagic vacuole. Further, lactate prevented H ₂ O ₂ -induced mitochondrial fission and maintained mitochondrial function by alleviating H ₂ O ₂ -induced mitochondrial membrane potential disruption and intracellular ROS generation. In contrast, application of 3-methyladenine, an inhibitor of autophagy, effectively weakened the protective effect of lactate against oxidative stress in vivo and in vitro. Taken together, all data in this study indicate that lactate protects against oxidative stress-induced retinal degeneration and preserves mitochondrial function by activating autophagy.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
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