ArticleInvestigative ophthalmology & visual science2023
Attenuation of Microglial Activation and Pyroptosis by Inhibition of P2X7 Pathway Promotes Photoreceptor Survival in Experimental Retinal Detachment.
Article in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Transcriptomic Profiling of the Human Retina Reveals Inflammatory and Metabolic Signatures Associated With Clinical Severity After Retinal Detachment.Investigative ophthalmology & visual science · 2026Article
- Targeting P2X7R Protects the Retina Against High-Altitude Hypoxia via NLRP3-Mediated Pyroptosis Suppression.Molecular neurobiology · 2026Article
- Targeting Apolipoprotein E4 rescues photoreceptor degeneration by inhibiting the disease-associated microglia activation in experimental retinal detachment.Journal of neuroinflammation · 2026Article
- Retinal gene therapy using epiretinal AAV-containing fibrin hydrogel implants.Science advances · 2025Article
- Review
- Ameboid Microglia as a Scavenger Role in Phagocytosis of Photoreceptor Outer Segment in an Experimental Retinal Detachment Model.Investigative ophthalmology & visual science · 2025Article
- Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment.Investigative ophthalmology & visual science · 2025Article
- The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Photoreceptor (PR) death is the ultimate cause of irreversible vision loss in retinal detachment (RD). Although microglial infiltration in the subretinal space (SRS) was observed after RD, the molecular mechanism underlying microglial activation and the outcomes of infiltrating microglia remain unclear. We aimed to uncover the mechanism of initiation of microglial activation to help explore potential therapy to promote PR survival. Methods: An RD model was conducted by injecting sodium hyaluronate into SRS of C57BL/6J wild type mice. Adenosine triphosphate (ATP) was measured by a ATP Microplate Assay Kit. Bioinformatics analysis was used to evaluate the upregulated receptor relating to ATP binding in human datasets and mouse transcriptomes of RD. Expression of P2X7, its downstream signaling pathways, and microglial pyroptosis were confirmed by qPCR, WB, and immunofluorescence in vivo and in vitro. The cell viability of PR was measured by cell counting kit-8. Brilliant Blue G, a P2X7 antagonist, was subretinally or intraperitoneally injected to inhibit microglial activation in vivo and was applied for microglia cell line treatment in vitro. The decrease in microglial activation and pyroptosis was detected by immunofluorescence and WB. The protective effect on PR was measured by hematoxylin and eosin staining, TUNEL assay, and electroretinogram analysis. Results: The results showed that extracellular ATP released in the SRS after RD triggered P2X7 activation and attracted microglia. The downstream cascade of inflammasome activation induced by P2X7 activation contributed to microglial pyroptosis and then to PR death. ATP-activated microglia led to PR death in vitro. P2X7 blockade rescued PR morphologically and functionally by inhibiting microglial activation and pyroptosis. Conclusions: These results elucidate that ATP-induced P2X7-mediated microglial activation leads to microglial pyroptosis, contributing to PR death. Appropriate inhibition of microglial pyroptosis might serve as a pharmacotherapeutic strategy for decreasing PR death in RD.
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