ArticleProceedings of the National Academy of Sciences of the United States of America2022
Compartmentalized citrullination in Muller glial endfeet during retinal degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Alexander disease mutations differentially sensitize glial fibrillary acidic protein (GFAP) to posttranslational modifications and network disruption by oxidants.Redox biology · 2026Article
- Dysfunction of Unc119, a Transducin-Binding Protein, Leads to Cone-Rod Dystrophy through Activating JAK-Stat and NF-κB Inflammatory Pathways in the Mouse Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.Scientific reports · 2025Article
- Identification of Biomarkers for Oxidative Stress in Age-Related Macular Degeneration: Combining Transcriptomics and Mendelian Randomization Analysis.Translational vision science & technology · 2025Article
- A Facile Strategy to Restore the Optic Nerve Functionality Using an Injectable Conducting Hydrogel.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration.iScience · 2025Article
- PARP inhibition preserves cone photoreceptors in rd2 retina.Acta neuropathologica communications · 2025Article
- JR5558 mice are a reliable model to investigate subretinal fibrosis.Scientific reports · 2024Article
- Article
- Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor.BMC genomics · 2023Article
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- Article
- A corneo-retinal hypercitrullination axis underlies ocular injury to nitrogen mustard.Experimental eye research · 2023Article
- Peptidyl arginine deiminase 4 deficiency protects against subretinal fibrosis by inhibiting Müller glial hypercitrullination.Journal of neuroscience research · 2023Article
- Article
- Organoid-derived human retinal progenitor cells promote early dedifferentiation of Müller glia in Royal College of Surgeons rats.International journal of ophthalmology · 2023Article
- Protein citrullination marks myelin protein aggregation and disease progression in mouse ALS models.Acta neuropathologica communications · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Muller glia (MG) play a central role in reactive gliosis, a stress response associated with rare and common retinal degenerative diseases, including age-related macular degeneration (AMD). The posttranslational modification citrullination targeting glial fibrillary acidic protein (GFAP) in MG was initially discovered in a panocular chemical injury model. Here, we report in the paradigms of retinal laser injury, a genetic model of spontaneous retinal degeneration (JR5558 mice) and human wet-AMD tissues that MG citrullination is broadly conserved. After laser injury, GFAP polymers that accumulate in reactive MG are citrullinated in MG endfeet and glial cell processes. The enzyme responsible for citrullination, peptidyl arginine deiminase-4 (PAD4), localizes to endfeet and associates with GFAP polymers. Glial cell-specific PAD4 deficiency attenuates retinal hypercitrullination in injured retinas, indicating PAD4 requirement for MG citrullination. In retinas of 1-mo-old JR5558 mice, hypercitrullinated GFAP and PAD4 accumulate in MG endfeet/cell processes in a lesion-specific manner. Finally, we show that human donor maculae from patients with wet-AMD also feature the canonical endfeet localization of hypercitrullinated GFAP. Thus, we propose that endfeet are a "citrullination bunker" that initiates and sustains citrullination in retinal degeneration.
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Registered trials
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