ArticleInvestigative ophthalmology & visual science2021
Differential and Altered Spatial Distribution of Complement Expression in Age-Related Macular Degeneration.
Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Deep-learning automated quantification of longitudinal OCT scans demonstrates reduced RPE loss rate, preservation of intact macular area and predictive value of isolated photoreceptor degeneration in geographic atrophy patients receiving C3 inhibition treatment.The British journal of ophthalmology · 2024Trial
- Article
- Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state.Acta neuropathologica communications · 2025Article
- A high-fat plus high-sucrose diet induces age-related macular degeneration in an experimental rabbit model.Disease models & mechanisms · 2024Article
- CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
- Gliosis-dependent expression of complement factor H truncated variants attenuates retinal neurodegeneration following ischemic injury.Journal of neuroinflammation · 2024Article
- Perspective from single-cell sequencing: Is inflammation in acute ischemic stroke beneficial or detrimental?CNS neuroscience & therapeutics · 2024Review
- Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.Human molecular genetics · 2023Article
- Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway.Immunological reviews · 2023Review
- Identification and Validation of an Aging-Associated circRNA-miRNA-mRNA Network in Neovascular Age-Related Macular Degeneration.Gerontology · 2023Article
- Relationships between Lipid-Related Metabolites and Age-Related Macular Degeneration Vary with Complement Genotype.Ophthalmology science · 2022Article
- Danicopan, an Oral Complement Factor D Inhibitor, Exhibits High and Sustained Exposure in Ocular Tissues in Preclinical Studies.Translational vision science & technology · 2022Article
- Local factor H production by human choroidal endothelial cells mitigates complement deposition: implications for macular degeneration.The Journal of pathology · 2022Article
- Exploring the pathogenesis of age-related macular degeneration: A review of the interplay between retinal pigment epithelium dysfunction and the innate immune system.Frontiers in neuroscience · 2022Review
- As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues.Frontiers in immunology · 2022Article
- Association of Serum Complement C1q and C3 Level with Age-Related Macular Degeneration in Women.Journal of inflammation research · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Dysregulation of the alternative complement pathway is a major pathogenic mechanism in age-related macular degeneration. We investigated whether locally synthesized complement components contribute to AMD by profiling complement expression in postmortem eyes with and without AMD. Methods: AMD severity grade 1 to 4 was determined by analysis of postmortem acquired fundus images and hematoxylin and eosin stained histological sections. TaqMan (donor eyes n = 39) and RNAscope/in situ hybridization (n = 10) were performed to detect complement mRNA. Meso scale discovery assay and Western blot (n = 31) were used to measure complement protein levels. Results: The levels of complement mRNA and protein expression were approximately 15- to 100-fold (P < 0.0001-0.001) higher in macular retinal pigment epithelium (RPE)/choroid tissue than in neural retina, regardless of AMD grade status. Complement mRNA and protein levels were modestly elevated in vitreous and the macular neural retina in eyes with geographic atrophy (GA), but not in eyes with early or intermediate AMD, compared to normal eyes. Alternative and classical pathway complement mRNAs (C3, CFB, CFH, CFI, C1QA) identified by RNAscope were conspicuous in areas of atrophy; in those areas C3 mRNA was observed in a subset of IBA1+ microglia or macrophages. Conclusions: We verified that RPE/choroid contains most ocular complement; thus RPE/choroid rather than the neural retina or vitreous is likely to be the key site for complement inhibition to treat GA or earlier stage of the disease. Outer retinal local production of complement mRNAs along with evidence of increased complement activation is a feature of GA.
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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.