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• W3177308137 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." @default.
• W3177308137 created "2021-07-05" @default.
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• W3177308137 date "2021-06-23" @default.
• W3177308137 modified "2023-10-17" @default.
• W3177308137 title "Differential and Altered Spatial Distribution of Complement Expression in Age-Related Macular Degeneration" @default.
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• W3177308137 doi "https://doi.org/10.1167/iovs.62.7.26" @default.
• W3177308137 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8237111" @default.
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• W3177308137 hasPublicationYear "2021" @default.
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