ArticleEye (London, England)2011
Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration.
Article in Eye (London, England), 2011. 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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Who cites it
47 citing papers in PubMed, 76 citations in OpenAlex.
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- Bradykinin B1 receptor signaling triggers complement activation on endothelial cells.Frontiers in immunology · 2025Article
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- Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.Clinical interventions in aging · 2024Review
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.Frontiers in immunology · 2023Review
- Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration.Frontiers in neuroscience · 2023Review
- Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells.Frontiers in immunology · 2023Article
- Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential.International journal of molecular sciences · 2022Review
- Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration.Experimental eye research · 2022Review
- Association of Blood Group Antigen CD59 with Disease.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2022Review
- Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.Journal of extracellular vesicles · 2021Article
- The innate immune system in diabetic retinopathy.Progress in retinal and eye research · 2021Review
- Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.Progress in retinal and eye research · 2021Review
- Complement System and Potential Therapeutics in Age-Related Macular Degeneration.International journal of molecular sciences · 2021Review
- The Long Pentraxin PTX3 as a New Biomarker and Pharmacological Target in Age-Related Macular Degeneration and Diabetic Retinopathy.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThere is evidence for complement dysfunction in age-related macular degeneration (AMD). Complement activation leads to formation of the membrane attack complex (MAC), known to assemble on retinal pigment epithelial (RPE) cells. Therefore, the effect of sub-lytic MAC on RPE cells was examined with regard to pro-inflammatory or pro-angiogenic mediators relevant in AMD.
methodsFor sub-lytic MAC induction, RPE cells were incubated with an antiserum to complement regulatory protein CD59, followed by normal human serum (NHS) to induce 5% cell death, measured by a viability assay. MAC formation was evaluated by immunofluorescence and FACS analysis. Interleukin (IL)-6, -8, monocytic chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Intracellular MCP-1 was analysed by immunofluorescence, vitronectin by western blotting, and gelatinolytic matrix metalloproteinases (MMPs) by zymography.
resultsIncubation of RPE cells with the CD59 antiserum followed by 5% NHS induced sub-lytic amounts of MAC, verified by FACS and immunofluorescence. This treatment stimulated the cells to release IL-6, -8, MCP-1, and VEGF. MCP-1 staining, production of vitronectin, and gelatinolytic MMPs were also elevated in response to sub-lytic MAC.
conclusionsMAC assembly on RPE cells increases the IL-6, -8, and MCP-1 production. Therefore, sub-lytic MAC might have a significant role in generating a pro-inflammatory microenvironment, contributing to the development of AMD. Enhanced vitronectin might be a protective mechanism against MAC deposition. In addition, the increased expression of gelatinolytic MMPs and pro-angiogenic VEGF may be associated with neovascular processes and late 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.