ArticleScientific reports2018
Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
- Deep-learning automated quantification of longitudinal OCT scans demonstrates reduced RPE loss rate, preservation of intact macular area and predictive value of isolated photoreceptor degeneration in geographic atrophy patients receiving C3 inhibition treatment.The British journal of ophthalmology · 2024Trial
- Pharmacological Characterization of a Novel Complement C3 Inhibitor Antibody Fragment.Ophthalmology and therapy · 2026Article
- Tropomyosin-Related Kinase Receptor Type B Agonism in Geographic Atrophy-The Translational Challenges from Preclinical Data to a First-in-Human Trial.Ophthalmology science · 2026Article
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- EREG-secreting THBS1Hepatobiliary surgery and nutrition · 2026Article
- Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.Genes · 2026Review
- Management of submacular hemorrhage: from a case report to a comprehensive review of current treatment strategies.International ophthalmology · 2026Review
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Efficacy and Safety of Efdamrofusp Alfa with Personalized Dosing Intervals in Neovascular Age-Related Macular Degeneration: A Phase II Trial.Ophthalmology science · 2026Article
- Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Clinical Trial Simulation in Geographic Atrophy: Patient, Caregiver, and Trial Site Staff Perspectives.Ophthalmology and therapy · 2025Article
- Geographic atrophy in Asia.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Decreased complement 4 and interleukin-10 as biomarkers in aqueous humour for non-exudative age-related macular degeneration: a case control study.Journal of translational medicine · 2025Article
- Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration.Pharmacology research & perspectives · 2025Article
- Fundus Autofluorescence Variation in Geographic Atrophy of Age-Related Macular Degeneration: A Clinicopathologic Correlation.Investigative ophthalmology & visual science · 2025Article
- Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.Translational vision science & technology · 2025Article
- Roles of MASP-1 and MASP-3 in the development of retinal degeneration in a murine model of dry age-related macular degeneration.Frontiers in immunology · 2025Article
- Complement C3 knockout protects photoreceptors in the sodium iodate model.Experimental eye research · 2025Article
- SLC16A8 is a causal contributor to age-related macular degeneration risk.NPJ genomic medicine · 2024Article
- The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment.Journal of neuroinflammation · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.
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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.