Background: The degeneration of retinal pigmented epithelium (RPE) cells results in severe diseases, such as age-related macular degeneration (AMD) that causes blindness in millions of individuals.
Results: We report that targeting GMP-AMP (cGAMP) synthase (cGAS) alleviates Alu RNA-induced immune responses and cytotoxicity in RPE. We find that the deletion of cGAS in RPE inhibits the Alu RNA-stimulated interferon production. cGAS deficiency also protects RPE from cell death triggered by Alu RNA. Importantly, two natural chemicals, epigallocatechin gallate (EGCG) and resveratrol (RSVL), are effective in suppressing the immunogenic and cytotoxic effect of Alu RNA in RPE.
Conclusions: Our findings further demonstrate the crucial role of cGAS in the Alu RNA-induced RPE damage and present EGCG and RSVL as potential therapies for AMD and other RPE degeneration-related conditions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310409 | PMC |
| http://dx.doi.org/10.1186/s13578-022-00854-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
cGAS inhibition alleviates Alu RNA-induced immune responses and cytotoxicity in retinal pigmented epithelium.
Cell Biosci
July 2022
Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing, 100730, China.
Background: The degeneration of retinal pigmented epithelium (RPE) cells results in severe diseases, such as age-related macular degeneration (AMD) that causes blindness in millions of individuals.
Results: We report that targeting GMP-AMP (cGAMP) synthase (cGAS) alleviates Alu RNA-induced immune responses and cytotoxicity in RPE. We find that the deletion of cGAS in RPE inhibits the Alu RNA-stimulated interferon production.
Identification of fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration.
Proc Natl Acad Sci U S A
October 2021
Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, VA 22901;
The atrophic form of age-related macular degeneration (dry AMD) affects nearly 200 million people worldwide. There is no Food and Drug Administration (FDA)-approved therapy for this disease, which is the leading cause of irreversible blindness among people over 50 y of age. Vision loss in dry AMD results from degeneration of the retinal pigmented epithelium (RPE).
View Article and Find Full Text PDFcomplementary DNA is enriched in atrophic macular degeneration and triggers retinal pigmented epithelium toxicity via cytosolic innate immunity.
Sci Adv
October 2021
Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, VA, USA.
Long interspersed nuclear element-1 (L1)–mediated reverse transcription (RT) of RNA into cytoplasmic complementary DNA (cDNA) has been implicated in retinal pigmented epithelium (RPE) degeneration. The mechanism of cDNA–induced cytotoxicity and its relevance to human disease are unknown. Here we report that cDNA is highly enriched in the RPE of human eyes with geographic atrophy, an untreatable form of age-related macular degeneration.
View Article and Find Full Text PDFCytoplasmic synthesis of endogenous complementary DNA via reverse transcription and implications in age-related macular degeneration.
Proc Natl Acad Sci U S A
February 2021
Center for Advanced Vision Science, School of Medicine, University of Virginia, Charlottesville, VA 22908;
retroelements propagate via retrotransposition by hijacking long interspersed nuclear element-1 (L1) reverse transcriptase (RT) and endonuclease activities. Reverse transcription of RNA into complementary DNA (cDNA) is presumed to occur exclusively in the nucleus at the genomic integration site. Whether cDNA is synthesized independently of genomic integration is unknown.
View Article and Find Full Text PDFLamivudine Inhibits RNA-induced Retinal Pigment Epithelium Degeneration via Anti-inflammatory and Anti-senescence Activities.
Transl Vis Sci Technol
July 2020
Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Purpose: Accumulation of the long noncoding element RNA activates the NLRP3 inflammasome and leads to retinal pigment epithelium (RPE) cell death, a key event in the pathogenesis of geographic atrophy during late-stage age-related macular degeneration. Lamivudine (3TC) is a nucleoside analog reverse transcriptase inhibitor known to inhibit the NLRP3 inflammasome. Currently, the intracellular response of the senescence marker p16 to the long noncoding RNA is being actively studied.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!