ArticleJournal of neuroinflammation2022
Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
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Who cites it
47 citing papers in PubMed, 56 citations in OpenAlex.
- Engineered exosomes encapsulated miR-218-5p alleviate the progression of PMRedox biology · 2026Article
- LPA1-Induced EMT of Retinal Pigment Epithelial Cells Promotes Subretinal Fibrosis via USP1-Mediated Deubiquitination and Stabilization of ZEB1.Investigative ophthalmology & visual science · 2026Article
- A Novel Ocular Fibrosis Signature for AMD Using the Two-Stage Laser-Induced Subretinal Fibrosis Mouse Model.Investigative ophthalmology & visual science · 2026Article
- Complement C5a Promotes Epithelial-Mesenchymal Transition in Pterygium via C5aR Activation.Investigative ophthalmology & visual science · 2026Article
- MSC-EVs attenuate subretinal fibrosis in choroidal neovascularization through miR-21-5p-mediated inhibition of EMT and MMT and suppression of inflammation.Journal of neuroinflammation · 2026Article
- Signals of Drug-Related Retinal Fibrosis: Findings From a 20-Year Disproportionality Analysis of Global Spontaneous Reports.Translational vision science & technology · 2026Article
- miR-214-3p Mediates Samarium Oxide-Induced Pulmonary Fibrosis by Targeting MAP2K3 via the MAPK Signaling Pathway.Toxics · 2026Article
- Insights into risk factors and interactive effects on epiretinal membrane development from the National Health and Nutrition Examination Survey.International journal of ophthalmology · 2026Article
- ROP16 Promotes Epithelial-Mesenchymal Transition-Like Changes in Ocular Toxoplasmosis via STAT3 and TGF-β1 Pathways.Transboundary and emerging diseases · 2026Article
- Targeting the neurovascular unit in retinal fibrosis: mechanisms and therapeutic perspectives.Frontiers in medicine · 2026Review
- Management of fibrosis in neovascular age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming.International journal of molecular sciences · 2025Article
- C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.Investigative ophthalmology & visual science · 2025Article
- Metformin inhibits subretinal fibrosis by activating Klotho by miR-126-5p.Cytotechnology · 2025Article
- Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.Biomolecules · 2025Review
- Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism.Medical microbiology and immunology · 2025Article
- Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion.Investigative ophthalmology & visual science · 2025Article
- Modic changes: From potential molecular mechanisms to future research directions (Review).Molecular medicine reports · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWe previously reported higher plasma levels of complement fragments C3a and C5a in neovascular Age-related Macular Degeneration (nAMD) patients with macular fibrosis. This study aimed to understand whether complement activation contributes to the development of macular fibrosis and the underlying mechanisms involved.
methodsComplement activation was blocked using a C5 neutralizing antibody (BB5.1) in C57BL/6J mice after induction of subretinal fibrosis using the two-stage laser protocol. Fibrotic lesions were examined 10 days after the 2nd laser through fundus examination and immunohistochemistry. The expression of C5aR in fibrotic lesions and retinal pigment epithelial (RPE) cultures were examined by confocal microscopy. Primary murine RPE cells were treated with C3a or C5a (10-100 ng/mL) or TGF-β2 (10 ng/mL). Epithelial-to-mesenchymal transition (EMT) was assessed through various readouts. The expression of E-cadherin, vimentin, fibronectin, α-SMA, Slug, ERK/AKT and pSMAD2/3 were determined by Western blot and immunocytochemistry. Collagen contraction and wound-healing assays were used as functional readouts of EMT. The production of IL-6, TGF-β1, TGF-β2 and VEGF by RPE cells were determined by ELISA. PMX53 was used to block C5aR in RPE cultures and in vivo in mice with subretinal fibrosis.
resultsExtensive C5b-9 deposition was detected at the site of subretinal fibrosis. BB5.1 treatment completely abrogated complement activation and significantly reduced subretinal fibrosis. C5aR was detected in RPE and infiltrating MHC-II
conclusionsComplement activation is critically involved in the development of subretinal fibrosis, partially through C5a-C5aR-mediated EMT in RPE cells. Targeting complement activation rather than C5a may be a novel approach for the management of macular fibrosis.
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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.