June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Heterochromatin suppresses oxidative stress-induced cGAS and STING expression in mouse RPE and retina
Author Affiliations & Notes
  • wei liu
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Zou Ming
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Ruili Qi
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Qin Ke
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • xingfei zhu
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • David W Li
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Lili Gong
    ZhongShan Ophthalmic Center,Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   wei liu National Natural Science Foundation of China (Grants 82070969, 81970787) , Code F (Financial Support), Natural Science Foundation of Guangdong Province of China (2021A1515011793), Code F (Financial Support); Zou Ming None; Ruili Qi None; Qin Ke None; xingfei zhu None; David Li None; Lili Gong None
  • Footnotes
    Support  National Natural Science Foundation of China (Grants 82070969, 81970787) and Natural Science Foundation of Guangdong Province of China (2021A1515011793)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3884 – A0086. doi:
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      wei liu, Zou Ming, Ruili Qi, Qin Ke, xingfei zhu, David W Li, Lili Gong; Heterochromatin suppresses oxidative stress-induced cGAS and STING expression in mouse RPE and retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3884 – A0086.

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

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Abstract

Purpose : Heterochromatin is a highly compact, transcription inert chromatin status. cGAS and STING are two key components mediating innate immune response, and are recently shown contributes to geographic atrophy (GA) . After analyzing the published transposase-accessible chromatin sequencing (ATAC-Seq) datasets , we found that STING gene loci exhibited decreased chromatin compaction in RPE of the GA patient. Therefore, we are aimed to investigate whether heterochromatin may regulate cGAS and STING expression upon oxidative stress

Methods : The in vivo oxidative stress was induce by intraperitoneal injection of sodium iodate (SI, 10-70 mg/kg). cGAS and STING expression were determined by qRT-PCR and western blot (WB) analysis in control (PBS-injected) or SI-injected mouse retina and RPE. Retina and RPE structure were asses by immunofluorescence and HE staining. cGAS and STING chromatin accessibility was assessed by the micrococcal nuclease (MNase) digestion assay. The in vivo effects of heterochromatin on cGAS and STING expression were determined in CBX5 knockout mice, in which the heterochromatin structure protein HP1α was depleted.

Results : Both cGAS and STING RNA and protein were upregulated in a dose-dependent manner in mouse retina and RPE. Decreased chromatin compaction were detected in both cGAS and STING gene loci upon SI injury. Increased cGAS, STING and the downstream IL6 and IL1β expression were detected in CBX5 knockout mice retina after SI injection. Depletion of this heterochromatin structure protein led to more severe retina destruction and IBA1-positive immune cell infiltration upon SI injury.

Conclusions : Heterochromatin represses cGAS and STING expression during oxidative injury. Our results suggest a potential role for targeting heterochromatin in the treatment of age-related macular degeneration (AMD).

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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