ArticleProceedings of the National Academy of Sciences of the United States of America2022
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.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Exploring the role of oxidative stress in retinal vein occlusion: an updated and comprehensive review on the pathophysiology and treatment perspectives.International ophthalmology · 2025Pooled it
- Identification of novel blood-borne soluble binding partners of factor H-related proteins.Scientific reports · 2026Article
- Granzyme B from mast cells contributes to choroidal neovascularization in a model of wet age-related macular degeneration.Frontiers in immunology · 2026Article
- De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa.Nature genetics · 2026Article
- Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes.Nature genetics · 2025Article
- Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration.Arthritis research & therapy · 2025Article
- De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.medRxiv : the preprint server for health sciences · 2025Article
- Elevation of ANXA1 associated with potential protective mechanism against ferroptosis and immune cell infiltration in age-related macular degeneration.European journal of medical research · 2024Article
- Redefining our vision: an updated guide to the ocular immune system.Nature reviews. Immunology · 2024Review
- Mast cells promote choroidal neovascularization in a model of age-related macular degeneration.Journal of neuroinflammation · 2024Article
- Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.Angiogenesis · 2024Article
- Mast cells in human choroid and their role in age-related macular degeneration (AMD).Clinical and experimental medicine · 2024Review
- Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.Clinical interventions in aging · 2024Review
- Review
- Choroidal Vasculature Changes in Age-Related Macular Degeneration: From a Molecular to a Clinical Perspective.International journal of molecular sciences · 2022Review
- Systematic Review of Proteomics in Age-Related Macular Degeneration and Pathway Analysis of Significant Protein Changes.Ophthalmology scienceReview
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Age-related macular degeneration (AMD) is a leading cause of visual loss. It has a strong genetic basis, and common haplotypes on chromosome (Chr) 1 (CFH Y402H variant) and on Chr10 (near HTRA1/ARMS2) contribute the most risk. Little is known about the early molecular and cellular processes in AMD, and we hypothesized that analyzing submacular tissue from older donors with genetic risk but without clinical features of AMD would provide biological insights. Therefore, we used mass spectrometry–based quantitative proteomics to compare the proteins in human submacular stromal tissue punches from donors who were homozygous for high-risk alleles at either Chr1 or Chr10 with those from donors who had protective haplotypes at these loci, all without clinical features of AMD. Additional comparisons were made with tissue from donors who were homozygous for high-risk Chr1 alleles and had early AMD. The Chr1 and Chr10 risk groups shared common changes compared with the low-risk group, particularly increased levels of mast cell–specific proteases, including tryptase, chymase, and carboxypeptidase A3. Histological analyses of submacular tissue from donors with genetic risk of AMD but without clinical features of AMD and from donors with Chr1 risk and AMD demonstrated increased mast cells, particularly the tryptase-positive/chymase-negative cells variety, along with increased levels of denatured collagen compared with tissue from low–genetic risk donors. We conclude that increased mast cell infiltration of the inner choroid, degranulation, and subsequent extracellular matrix remodeling are early events in AMD pathogenesis and represent a unifying mechanistic link between Chr1- and Chr10-mediated AMD.
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Registered trials
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