ArticleThe Journal of experimental medicine2019
C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.Eye (London, England) · 2023Trial
- Inflammatory Markers and Disease Progression in Moderate-Stage Retinitis Pigmentosa: Longitudinal Analysis from the Retinitis Pigmentosa Progression and Inflammatory Marker Registry Study.Ophthalmology science · 2026Article
- Management of full-thickness macular holes in patients with retinitis pigmentosa - a case series of 5 patients operated with pars plana vitrectomy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Myd88 Deficiency Accelerates Retinal Degeneration and Alters Microglial Dynamics in a Mouse Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Discovery-Driven Plasma Proteomics Identifies a Multi-Protein Signature for Amyloid PET Positivity: A Machine Learning Analysis of the Bio-Hermes Cohort.International journal of molecular sciences · 2026Article
- TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa.Science advances · 2026Article
- Infiltrating monocytes augment alternative complement activation and exacerbate inherited retinal degeneration in a mouse model.Research square · 2026Article
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- The Arp2/3 complex is required for in situ haptotactic response of microglia to iC3b.EMBO reports · 2026Article
- Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.Genes · 2026Review
- Targeted Ferroptosis Improves RPE Phagocytosis via MERTK/NFE2L2/HMOX1 Axis to Alleviate Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Immunometabolic Regulation of Neuroinflammation in Retinitis Pigmentosa: Roles of Microglia, Müller Glia, and Regulated Cell Death.Biomolecules · 2026Review
- Exploring retinal microglia: development, degeneration, and iPSC-derived model systems.Brain structure & function · 2026Review
- Principles of resident tissue macrophages revealed by the eye.Advances in immunology · 2026Review
- Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.Molecular therapy. Methods & clinical development · 2025Article
- Transcriptional downregulation of rhodopsin is associated with desensitization of rods to light-induced damage in a murine model of retinitis pigmentosa.Human molecular genetics · 2025Article
- Macrophage/microglia-dependent mechanisms drive retinal pigment epithelium regeneration in zebrafish.Cell reports · 2025Article
- Preclinical Evaluation of Pitavastatin Nanoparticles for Preserving Cone Photoreceptors in Mouse Models of RP.Investigative ophthalmology & visual science · 2025Article
- S-ketamine exposure in early postnatal period induces social deficit mediated by excessive microglial synaptic pruning.Molecular psychiatry · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Complement activation has been implicated as contributing to neurodegeneration in retinal and brain pathologies, but its role in retinitis pigmentosa (RP), an inherited and largely incurable photoreceptor degenerative disease, is unclear. We found that multiple complement components were markedly up-regulated in retinas with human RP and the rd10 mouse model, coinciding spatiotemporally with photoreceptor degeneration, with increased C3 expression and activation localizing to activated retinal microglia. Genetic ablation of C3 accelerated structural and functional photoreceptor degeneration and altered retinal inflammatory gene expression. These phenotypes were recapitulated by genetic deletion of CR3, a microglia-expressed receptor for the C3 activation product iC3b, implicating C3-CR3 signaling as a regulator of microglia-photoreceptor interactions. Deficiency of C3 or CR3 decreased microglial phagocytosis of apoptotic photoreceptors and increased microglial neurotoxicity to photoreceptors, demonstrating a novel adaptive role for complement-mediated microglial clearance of apoptotic photoreceptors in RP. These homeostatic neuroinflammatory mechanisms are relevant to the design and interpretation of immunomodulatory therapeutic approaches to retinal degenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.