ArticleThe Journal of pathology2022
Local factor H production by human choroidal endothelial cells mitigates complement deposition: implications for macular degeneration.
Article in The Journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Insights into the modulation of age-related macular degeneration: Molecular and systems-level perspectives.Acta ophthalmologica · 2026Article
- The Biochemical and Genetic Architecture of Geographic Atrophy: The Role of the FHL-1/CFH Axis and the Paradigm of RNA Interference Therapeutics.Biomedicines · 2026Review
- GWAS Meta-analysis Identifies Novel Associated Loci and Points to Causal Tissues in Central Serous Chorioretinopathy.medRxiv : the preprint server for health sciences · 2026Article
- From Tears to Toxins: Mapping Antibiotic Passage Through the Eye-Liver Axis.Antibiotics (Basel, Switzerland) · 2025Review
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration.Acta biomaterialia · 2025Article
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Comparative analysis of In vivo endothelial cell translatomes across central nervous system vascular beds.Experimental eye research · 2024Article
- Complement C5/C5a in the diagnosis and treatment of GravesZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
- Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.Clinical interventions in aging · 2024Review
- Transcriptomic and Chromatin Accessibility Analysis of the Human Macular and Peripheral Retinal Pigment Epithelium at the Single-Cell Level.The American journal of pathology · 2023Article
- Location of Retinal Pigment Epithelial Cells in the Eye Is Critical to Their Function.The American journal of pathology · 2023Article
- AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.Investigative ophthalmology & visual science · 2023Article
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- Review
- Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the alternative complement pathway is an initiating event in the pathology of age-related macular degeneration (AMD). Unchecked complement activation leads to the formation of a pro-lytic pore, the membrane attack complex (MAC). MAC deposition is observed on the choriocapillaris of AMD patients and likely causes lysis of choroidal endothelial cells (CECs). Complement factor H (FH, encoded by the gene CFH) is an inhibitor of complement. Both loss of function of FH and reduced choroidal levels of FH have been reported in AMD. It is plausible that reduced local FH availability promotes MAC deposition on CECs. FH is produced primarily in the liver; however, cells including the retinal pigment epithelium can produce FH locally. We hypothesized that CECs produce FH locally to protect against MAC deposition. We aimed to investigate the effect of reduced FH levels in the choroid to determine whether increasing local FH could protect CECs from MAC deposition. We demonstrated that siRNA knockdown of FH (CFH) in human immortalized CECs results in increased MAC deposition. We generated AMD iPSC-derived CECs and found that overexpression of FH protects against MAC deposition. These results suggest that local CEC-produced FH protects against MAC deposition, and that increasing local FH protein may be beneficial in limiting MAC deposition in AMD. © 2022 The Pathological Society of Great Britain and Ireland.
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