cGAS inhibition alleviates Alu RNA-induced immune responses and cytotoxicity in retinal pigmented epithelium

cGAS 抑制可减轻 Alu RNA 诱导的视网膜色素上皮免疫反应和细胞毒性

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作者:Jing Li #, Feng Zhang #, Wei Bian, Yanyun Chen, Jianying Liu, Zhenyu Liu, Ying Xiong, Xiuhua Wan

Background

The degeneration of retinal pigmented epithelium (RPE) cells

Conclusions

Our findings further demonstrate the crucial role of cGAS in the Alu RNA-induced RPE damage and present EGCG and RSVL as potential therapies for AMD and other RPE degeneration-related conditions.

Results

We report that targeting GMP-AMP (cGAMP) synthase (cGAS) alleviates Alu RNA-induced immune responses and cytotoxicity in RPE. We find that the deletion of cGAS in RPE inhibits the Alu RNA-stimulated interferon production. cGAS deficiency also protects RPE from cell death triggered by Alu RNA. Importantly, two natural chemicals, epigallocatechin gallate (EGCG) and resveratrol (RSVL), are effective in suppressing the immunogenic and cytotoxic effect of Alu RNA in RPE. Conclusions: Our findings further demonstrate the crucial role of cGAS in the Alu RNA-induced RPE damage and present EGCG and RSVL as potential therapies for AMD and other RPE degeneration-related conditions.

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