AlphaA-Crystallin Modulates cGAS/STING Pathway to Regulate the Immune Microenvironment in the Ocular Lens

Abstract

Purpose : cGAS-STING pathway plays an important role in innate immunity. Previous studies have shown that activation of cGAS-STING is involved in regulating tumor microenvironment. Our recent studies reveal that activation of this pathway is implicated in the pathogenesis of age-related macular degeneration (Zou et al., 2022, Cell Death & Differentiation and Free Radical Biology & Medicine). Whether this pathway also plays a role in lens pathogenesis is the subject of the present study.

Methods : FHL124 cells were used for the testing system. Both empty vector and alphaA-crystallin expression constructs were transferred into FHL124 cells, and the stable lines were established. Glucose oxidase was used to treat the above stable lines of cells and to generate oxidative stress insult. Changes of the cGAS-STING pathway components were analyzed with QRT-PCR and Western blot analysis.

Results : In aA-crystallin overexpression FHL124 cells, the protein expression level of STING were downregulated to less than 50% but only slight change in the expression level of cGAS was observed. So is true in the changes of TBK1, IRF3 and p65 expression levels. The phosphorylation levels of TBK1 and p65 in aA-crystallin overexpression FHL124 cells displayed significant decrease. Under stimulation of glucose oxidase, the major signal components of the cGAS-STING pathway were lightly upregulated.

Conclusions : The cGAS/STING pathway regulates oxidative stress-induced inflammatory response through activation of the NF-kB, and aA-crystallin suppresses activation of this pathway to inhibit oxidative stress-induced inflammatory response.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.