ArticleInvestigative ophthalmology & visual science2025
Complement C3 Activation in the Human Retinal Pigment Epithelium.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review.Redox biology · 2026Review
- Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.Frontiers in medicine · 2026Review
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Authors and funding
11 authors.
Funding
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Abstract
Purpose: Epithelial maturation is essential for the specificity and functionality of retinal pigment epithelial (RPE) cell models. This study investigates how different maturation conditions shape RPE characteristics and cellular complement biology in two commonly used in vitro models: ARPE-19 and induced pluripotent stem cell-derived RPE (iPSC-RPE). Methods: ARPE-19 and iPSC-RPE cells were cultured under low maturation (LM) or high maturation (HM) conditions. Phenotype, RPE marker expression, and functional properties were assessed, and expression of local complement components was analyzed at the transcript, protein, and secretion levels. Intracellular complement C3 processing was characterized using epitope-specific antibodies. Results: HM conditions enhanced epithelial features in both models, with HM iPSC-RPE displaying enhanced apical localization of RPE markers, polarity, reduced cilia length, and higher transepithelial resistance. Expression and secretion of complement components C3, FB, FH/FHL-1, and FI, as well as FH staining patterns, varied with maturation condition. HM iPSC-RPE secreted increased levels of C3a, C3(H2O), and iC3b, whereas LM cells retained C3 fragments intracellularly. Western blotting and immunostaining revealed maturation-dependent C3 fragment profiles, with apical localization of C3 and intracellular presence of the intact C3 β chain in HM iPSC-RPE, while C3 fragments were present in LM and ARPE-19 cells. Conclusions: HM iPSC-RPE cells most closely mimic native RPE features and provide a robust model for in vitro studies. RPE cells exhibit cell-autonomous complement production and maturation-dependent C3 activation profiles, providing a foundation for future studies on C3 functionality in RPE homeostasis and retinal degeneration.
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