ArticleScientific reports2018
C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.Molecular therapy. Nucleic acids · 2026Article
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism.Medical microbiology and immunology · 2025Article
- Article
- Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.Investigative ophthalmology & visual science · 2025Article
- Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.Stem cell reports · 2025Article
- C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.Investigative ophthalmology & visual science · 2025Article
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.JCI insight · 2024Article
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.Frontiers in genetics · 2024Article
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.bioRxiv : the preprint server for biology · 2023Article
- Article
- Qihuang Granule protects the retinal pigment epithelium from oxidative stress via regulation of the alternative complement pathway.BMC complementary medicine and therapies · 2023Article
- Disturbed Matrix Metalloproteinases Activity in Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023Review
- Systems genomics in age-related macular degeneration.Experimental eye research · 2022Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration.Journal of neuroinflammation · 2022Article
- Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The mechanisms that connect complement system activation and basal deposit formation in early stages of age-related macular degeneration (AMD) are insufficiently understood, which complicates the design of efficient therapies to prevent disease progression. Using human fetal (hf) retinal pigment epithelial (RPE) cells, we have established an in vitro model to investigate the effect of complement C3a on RPE cells and its role in the formation of sub-RPE deposits. The results of these studies revealed that C3a produced after C3 activation is sufficient to induce the formation of sub-RPE deposits via complement-driven proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition of collagens IV and VI underneath the RPE, and impairs the extracellular matrix (ECM) turnover by increased MMP-2 activity, all mediated by downregulation of the ubiquitin proteasome pathway (UPP). The formation of basal deposits can be prevented by the addition of a C3aR antagonist, which restores the UPP activity and ECM turnover. These findings indicate that the cell-based model can be used to test potential therapeutic agents in vitro. The data suggest that modulation of C3aR-mediated events could be a therapeutic approach for treatment of early 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.