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Recent studies have demonstrated that neuroglial vascular unit (NGVU) injury leads to distinct fundus changes in DR, including exudates, cotton\u2010fluff spots, microangiomas, hemorrhages, and neovascularization. Currently, the primary clinical treatment options primarily target retinal microvascular degeneration during the middle and late stages of DR through techniques such as retinal laser photocoagulation, antivascular endothelial growth factor (VEGF) therapy, and vitrectomy. However, progression to these stages often results in irreversible damage to visual acuity with limited treatment efficacy. In recent years, relevant research has confirmed that NGVU injury occurs prior to retinal microangiopathy in patients with DR, and it is closely associated with impaired visual function. Therefore, targeting NGVU holds potential for future therapeutic interventions aimed at preventing and treating early\u2010stage DR. This review identifies six key molecular targets (P2X7 receptor, NLRP3 inflammasome, retinal microglial cell necroptosis pathway, spermine oxidase, and AQP4\u2010AS1 lncRNA) that mitigate NGVU dysfunction in preclinical models. Literature search was conducted in PubMed\/Embase using keywords \u201cdiabetic retinopathy,\u201d \u201cneuroglial vascular unit,\u201d and \u201ctargeted therapy\u201d (2018\u20132024), focusing on preclinical studies with in vivo efficacy data.<\/jats:p>","DOI":"10.1155\/jdr\/6922946","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:47:28Z","timestamp":1765975648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting Retinal Neuroglial Vascular Unit Damage: Novel Therapeutic Strategies for Early\u2010Stage Diabetic Retinopathy"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-9053","authenticated-orcid":false,"given":"Xiaodong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0111-7419","authenticated-orcid":false,"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1909"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/08820538.2021.1962920"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106066"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22169050"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.09.013"},{"key":"e_1_2_13_8_2","first-page":"1309","article-title":"Research Progress in the Prevention and Treatment of Diabetic Retinopathy Based on Retinal Neurovascular Unit Damage and Its Coupling Imbalance","volume":"22","author":"Li B. 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