ArticleProceedings of the National Academy of Sciences of the United States of America2024
Microglial cGAS-STING signaling underlies glaucoma pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.Neural regeneration research · 2026Article
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.Neural regeneration research · 2026Article
- Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.The EMBO journal · 2026Article
- Age-associated decline of Lamtor5 drives immunosenescence and systemic aging via cGAS-mediated paracrine inflammation.Cell death and differentiation · 2026Article
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- A dual-responsive CO-releasing nanogel ameliorates retinal ischemia-reperfusion injury by restoring mitochondrial homeostasis and attenuating cGAS-STING pathway activation.Materials today. Bio · 2026Article
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- Plasma-aqueous dual-fluid NEAT1/miR-93-5p axis may be involved in retinal ganglion cell degeneration in glaucoma: mechanistic dissection and diagnostic model construction.Scientific reports · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Dual immune armies in glaucoma: microglia and monocyte-derived macrophages.Frontiers in immunology · 2026Review
- Sterile inflammation in LHON: mitochondrial stress, innate immune signaling, and implications for AAV gene therapy.Frontiers in immunology · 2026Review
- Alpinetin Nanoparticles Alleviate Optic Nerve Injury Induced by Acute Glaucoma via LRP1-PPARγ Mediated Regulation of Microglial Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Urea functions as a risk signal driving astrocyte-mediated neuroinflammation following stroke.Journal of neuroinflammation · 2025Article
- Characterization of the microbial profile in tears of patients with primary open-angle glaucoma: results from a pilot study.Scientific reports · 2025Article
- cGAS-STING pathway-mediated inflammatory response and its role in corneal fibrosis mechanisms.Molecular biology reports · 2025Review
- Genetically Predicted Immunocyte Phenotypes as Risk and Protective Factors in Glaucoma: An Exploratory Bidirectional Mendelian Randomization Study.Translational vision science & technology · 2025Article
- Restoring AIBP expression in the retina provides neuroprotection in glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis.Investigative ophthalmology & visual science · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Characterized by progressive degeneration of retinal ganglion cells (RGCs) and vision loss, glaucoma is the primary cause of irreversible blindness, incurable and affecting over 78 million patients. However, pathogenic mechanisms leading to glaucoma-induced RGC loss are incompletely understood. Unexpectedly, we found that cGAS-STING (2'3'-cyclic GMP-AMP-stimulator of interferon genes) signaling, which surveils displaced double-stranded DNA (dsDNA) in the cytosol and initiates innate immune responses, was robustly activated during glaucoma in retinal microglia in distinct murine models. Global or microglial deletion of STING markedly relieved glaucoma symptoms and protected RGC degeneration and vision loss, while mice bearing genetic cGAS-STING supersensitivity aggravated retinal neuroinflammation and RGC loss. Mechanistically, dsDNA from tissue injury activated microglial cGAS-STING signaling, causing deleterious macroglia reactivity in retinas by cytokine-mediated microglia-macroglia interactions, progressively driving apoptotic death of RGCs. Remarkably, preclinical investigations of targeting cGAS-STING signaling by intraocular injection of TBK1i or anti-IFNAR1 antibody prevented glaucoma-induced losses of RGCs and vision. Therefore, we unravel an essential role of cGAS-STING signaling underlying glaucoma pathogenesis and suggest promising therapeutic strategies for treating this devastating disease.
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