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To better understand the heterogeneous pathogenesis of ARC and identify potential therapeutic targets, we generate a comprehensive atlas of age\u2010related cataracts at a single\u2010cell resolution, encompassing three disease states\u2014mild cataract group (Mild), severe cortical cataract group (Severe_C), and severe nuclear cataract group (Severe_N)\u2014with a total of 230\u00a0838 lens epithelial cells (LECs) derived from the lens capsules of 554 patients. We find that ARC involves seven distinct lens capsule cell types, with notable differences in cellular composition and functional states across disease severities. Unexpectedly, we discover that neuronal axon\u2010like structures ingrowth into the lens is associated with cataractogenesis and its progression. All three disease groups show significant enrichment of the neurotrophic SLIT\u2010ROBO signaling pathway. Cluster 0 exhibits high expression of the neurotrophic factor NRG1, which forms a stable ligand\u2010receptor axis with the ERBB3 receptor on sympathetic neurons. These findings not only reveal the heterogeneity of ARC at the levels of cellular composition and signaling pathways but also suggest that neuro\u2010lens interactions may play a critical role in cataract development. This provides a new perspective for understanding the pathogenesis of age\u2010related cataracts.<\/jats:p>","DOI":"10.1002\/advs.76532","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:05:14Z","timestamp":1785938714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deconstruction of Human Age\u2010Related Cataract Capsules Defines Aging"],"prefix":"10.1002","volume":"13","author":[{"given":"Qiaomei","family":"Tang","sequence":"first","affiliation":[{"name":"Eye Center School of Medicine The Second Affiliated Hospital Zhejiang Provincial Key Lab of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Tong","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Center For Stem Cell and Tissue Engineering School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine &amp; Orthopedic Surgery The Second Affiliated Hospital and Liangzhu Laboratory School of Medicine Zhejiang University  Hangzhou China"},{"name":"Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province Department of Clinical Medicine School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silong","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center School of Medicine The Second Affiliated Hospital Zhejiang Provincial Key Lab of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Guo","sequence":"additional","affiliation":[{"name":"Eye Center School of Medicine The Second Affiliated Hospital Zhejiang Provincial Key Lab of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Jiande Branch The Second Affiliated Hospital School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yao","sequence":"additional","affiliation":[{"name":"Eye Center School of Medicine The Second Affiliated Hospital Zhejiang Provincial Key Lab of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Yin","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Center For Stem Cell and Tissue Engineering School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-5286","authenticated-orcid":false,"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Center For Stem Cell and Tissue Engineering School of Medicine Zhejiang University  Hangzhou China"},{"name":"Department of Sports Medicine &amp; Orthopedic Surgery The Second Affiliated Hospital and Liangzhu Laboratory School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Yu","sequence":"additional","affiliation":[{"name":"Eye Center School of Medicine The Second Affiliated Hospital Zhejiang Provincial Key Lab of Ophthalmology Zhejiang Provincial Clinical Research Center for Eye Diseases Zhejiang Provincial Engineering Institute on Eye Diseases Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30489-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)01839\u20106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010020\u20100806\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.1.169"},{"key":"e_1_2_10_6_1","first-page":"93","article-title":"Lens Epithelium In Senile Cataract","volume":"93","author":"Tseng S. 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