June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
AlphaA-Crystallin Modulates cGAS/STING Pathway to Regulate the Immune Microenvironment in the Ocular Lens
Author Affiliations & Notes
  • Shuyu Zheng
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Jialing Fu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Yan Wang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Jingmiao Wang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • yuan xiao
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • LAN ZHANG
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Xuebin Hu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • yuwen gan
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Xingmiao Liang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • David W Li
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Shuyu Zheng None; Jialing Fu None; Yan Wang None; Jingmiao Wang None; yuan xiao None; LAN ZHANG None; Xuebin Hu None; yuwen gan None; Xingmiao Liang None; David Li None
  • Footnotes
    Support  NSFC#82271071, #81970787, #81770910; NSF-Guangdong Province and Guangzhou City Joint Program#20191515120014; ZOC-SKLO#3030901010111
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4133. doi:
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    • Get Citation

      Shuyu Zheng, Jialing Fu, Yan Wang, Jingmiao Wang, yuan xiao, LAN ZHANG, Xuebin Hu, yuwen gan, Xingmiao Liang, David W Li; AlphaA-Crystallin Modulates cGAS/STING Pathway to Regulate the Immune Microenvironment in the Ocular Lens. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4133.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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