ArticleInvestigative ophthalmology & visual science2012
A novel role of complement in retinal degeneration.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.Eye (London, England) · 2023Trial
- Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16.Ophthalmology · 2018Trial
- Review
- Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion.Investigative ophthalmology & visual science · 2025Article
- C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.Investigative ophthalmology & visual science · 2025Article
- Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and Where We Need to Go.American journal of ophthalmology · 2024Review
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Cellular and Molecular Triggers of Retinal Regeneration in Amphibians.Life (Basel, Switzerland) · 2023Review
- Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.Immunological reviews · 2023Review
- Geographic atrophy: pathophysiology and current therapeutic strategies.Frontiers in ophthalmology · 2023Review
- Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina.Molecular vision · 2023Article
- C1q and the classical complement cascade in geographic atrophy secondary to age-related macular degeneration.International journal of retina and vitreous · 2022Review
- The complement C3a-C3aR and C5a-C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF-κB signaling.Experimental and therapeutic medicine · 2022Article
- Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Systematic Review.Ophthalmology science · 2022Article
- Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.Progress in retinal and eye research · 2021Review
- Complement Inhibition for Geographic Atrophy: A Tempting Target with Mixed Results.Journal of clinical medicine · 2021Article
- Distinct effects of complement and of NLRP3- and non-NLRP3 inflammasomes for choroidal neovascularization.eLife · 2020Article
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe association of single nucleotide polymorphisms of components of the complement alternative pathway with the risk of age-related macular degeneration (AMD) indicates that complement signaling plays an important role in retinal physiology. How genetic variation leads to retinal degeneration is unknown. It has been assumed that complement activation augments immune responses, which in turn initiate AMD pathogenesis. To better understand the relationship between complement and the outer retina, we examined mice lacking the main complement component C3 and the receptors for complement activation fragments C3a (C3aR) and/or C5a (C5aR).
methodsComplement mutant mice were studied along with wild-type (WT) littermates from 6 weeks to 14 months of age. Strobe flash electroretinography (ERG) was used to examine outer retinal function and a dc-ERG technique was used to measure ERG components generated by the retinal pigment epithelium. Retinas were examined by histology, immunohistochemistry, and biochemistry.
resultsMice lacking C3aR and/or C5aR developed early onset and progressive retinal degeneration, accompanied by cleaved caspase-3 upregulation. Genetic deletion of C3aR and/or C5aR led to cell-specific defects that matched the cellular localization of these receptors in the WT retina. Compared to WT, C3aR(-/-) and C3aR(-/-)C5aR(-/-) mice showed increased retinal dysfunction upon light exposure. C3aR(-/-)C5aR(-/-) mice immunized with 4-hydroxynonenal-adducted protein developed severe retinal impairment unrelated to immune response.
conclusionsC3aR- and C5aR-mediated signaling was necessary to maintain normal retinal function and structure. These receptors may be important biomarkers for predicting retinal degeneration including AMD.
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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.