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However, the impact of myopia on DR and its underlying mechanisms remains unclear. Herein, by establishing a form\u2010deprivation myopia (FDM) and lens\u2010induced myopia (LIM) models in diabetic db\/db mice, a significant reduction of retinal vascular lesions is identified in db\/db mice after myopia modeling. Single\u2010cell transcriptomic analysis further reveals elevated expression of Nervous system nuclear protein induced by axotomy 1 (Nna1) in M\u00fcller cells of db\/db mice subjected to FDM compared to db\/db alone, alongside decreased Nna1 expression in db\/db compared to db\/m mice. Knockdown of Nna1 in FDM\u2010treated db\/db eyes reverses the protective effects of myopia on DR. Transcriptomic profiling links reduced Nna1 expression to enhanced apoptotic and autophagic signaling pathways in M\u00fcller cells. Further in vivo and in vitro experiments confirm that Nna1 overexpression suppresses microtubule hyper\u2010glutamylation, thereby reducing autophagy and apoptosis levels in M\u00fcller cells, and ameliorating DR progression. These findings suggest that Nna1 may play a key role in protecting M\u00fcller cells and maintaining the integrity of the neurovascular unit, thereby contributing to the protective effects of myopia in DR and representing a potential molecular target for early intervention and treatment of DR.<\/jats:p>","DOI":"10.1002\/advs.202500438","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T13:34:24Z","timestamp":1762349664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010Cell RNA Sequencing of Retina Reveals Nna1 Upregulation in Myopic Diabetic Retinopathy as a Protective Factor Against Diabetic Damage"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8981-5681","authenticated-orcid":false,"given":"Lihui","family":"Xie","sequence":"first","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Cai","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-334X","authenticated-orcid":false,"given":"Huizhuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62124-3"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010122"},{"key":"e_1_2_9_4_1","volume":"3","author":"Martinez\u2010Zapata M. 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