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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the aging population globally. Although genome-wide association studies (GWAS) have identified many AMD susceptibility loci, the genes and mechanisms underlying many of these associations remain unresolved. Here, we integrated expression quantitative trait locus (eQTL) data with AMD GWAS to prioritize nine putative genes. Through in vivo screening in zebrafish, we demonstrated that the downregulation of\n                    <jats:italic toggle=\"yes\">cnn2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">sarm1<\/jats:italic>\n                    expression led to ocular structural abnormalities and visual functional impairment. Subsequent mouse model studies confirmed that\n                    <jats:italic toggle=\"yes\">Cnn2<\/jats:italic>\n                    deficiency affected photoreceptor structure and function, impaired contrast sensitivity, and caused abnormalities in cone cell immunostaining. Given that\n                    <jats:italic toggle=\"yes\">CNN2<\/jats:italic>\n                    is predominantly expressed in endothelial cells, we propose that endothelial dysfunction may cascade to impair photoreceptor function. Collectively, through in silico prioritization and cross-species functional characterization, we identify\n                    <jats:italic toggle=\"yes\">CNN2<\/jats:italic>\n                    as a candidate susceptibility gene in AMD pathogenesis, providing vital underlying mechanistic insights.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2533682123","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:36:43Z","timestamp":1788370603000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Genetic evidence and cross-species functional characterization implicate\n                    <i>CNN2<\/i>\n                    in age-related macular degeneration 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