June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Innate Immune Mechanisms in Oxidative Retinal Damage
Author Affiliations & Notes
  • Nagaraj Kerur
    The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Daipayan Banerjee
    Aravind Medical Research Foundation, Madurai, India
  • Aman Kumar
    The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Daniel Hunter Biddle
    The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Nagaraj Kerur University of Virginia, University of Kentucky, Code P (Patent); Daipayan Banerjee University of Virginia, Code P (Patent); Aman Kumar None; Daniel Biddle None
  • Footnotes
    Support  This project was supported by grants to N.K. from NIH (R00EY024336, R01AI14874, R21EY030651, and R01AI14874-03S1) and The Ohio Lions Eye Research Foundation.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3043 – F0414. doi:
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    • Get Citation

      Nagaraj Kerur, Daipayan Banerjee, Aman Kumar, Daniel Hunter Biddle; Innate Immune Mechanisms in Oxidative Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3043 – F0414.

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

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Abstract

Purpose : Clinical and experimental evidence implicate oxidative stress in the pathogenesis of multiple vision threatening diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Oxidative stress damages biological macromolecules such as proteins, lipids, and DNA. The pathological consequences of oxidative damage to lipids and proteins in the retina have been well studied. However, whether oxidative damage to DNA – which is elevated in AMD, DR, and glaucoma eye specimens, as well as in experimental animal models – contributes to retinal pathology remains a major gap in the knowledge. The goal of this study is to examine the hypothesis cGAS which is activated by damages self-DNA, plays crucial roles in mediating oxidative retinal damage.

Methods : Human primary RPE and THP1 cells were exposed to oxidative stress by incubating with sodium iodate and cigarette smoke extract. cGAS pathway was blocking by either lentivirus delivered shRNA or CRISPR/Cas9. Activation of cGAS pathway was assessed by examining signaling activity downstream of cGAS by immunoblotting for phospho-STAT2 (pSTAT2), phosphor-ATM (pATM) and phospho-CHK2 (pCHK2).

Results : Exposure to oxidative stress via incubation with sodium iodate and cigarette smoke extract activated type I interferons and DNA damage signaling as demonstrated by induction of pSTAT2, pATM and pCHK2. These signaling activities were dampened in cGAS knockdown and knockout cells.

Conclusions : Our results suggest that cGAS pathway is activated by oxidative stress providing rationale for detailed analysis of role of cGAS in oxidative retinal damage.

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

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