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Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA

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Jian-Xing Ma

https://orcid.org/0000-0001-8815-1716

Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27101, USA

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Adam S Duerfeldt

*Author for correspondence:

E-mail Address: aduerfel@umn.edu

https://orcid.org/0000-0002-3130-9890

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA

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Published Online:11 May 2023https://doi.org/10.4155/fmc-2022-0301

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Abstract

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS–STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS–STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining the roles of this system in the retina is expected to reveal new disease pathology and novel therapeutic approaches.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 8

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History

Received 8 December 2022

Accepted 28 March 2023

Published online 11 May 2023

Published in print April 2023

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Keywords

Author contributions

B Hu: writing and editing. JX Ma: writing and editing; AS Duerfeldt: writing and editing.

Financial & competing interests disclosure

AS Duerfeldt and JX Ma are cofounders of Excitant Therapeutics. B Hu is a graduate student at the University of Minnesota in the Department of Medicinal Chemistry and is supported in part by the National Eye Institute of the National Institutes of Health grant number EY030472 (AS Duerfeldt and JX Ma). Additional support is provided by National Institutes of Health grant numbers EY033330 and EY019309 (JX Ma). The content included in this manuscript does not necessarily reflect the position or the policy of the federal government, and no official endorsement should be inferred. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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The cGAS–STING pathway in diabetic retinopathy and age-related macular degeneration

Abstract

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