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We validated this hypothesis using endothelial cells in vitro, and immunohistochemistry of disrupted photoreceptor ribbon synapses in mouse and human diabetic retinas. In addition, glutamine deprivation increased the expression of apoptotic genes in endothelial cells. At 6 mo, we observed significant down-regulation of angiogenic pathways and elevated profibrotic markers. Our results suggest that dysfunction of the metabolic ecosystem linking the M\u00fcller\u2013photoreceptor\u2013endothelial cells is central to the early stages of DRD pathogenesis, impacting photoreceptor synapses and endothelial cells, before the appearance of the classic microvascular features of DR.<\/jats:p>","DOI":"10.26508\/lsa.202503434","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T07:21:26Z","timestamp":1762932086000},"page":"e202503434","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["M\u00fcller cell glutamine metabolism links photoreceptor and endothelial injury in diabetic retinopathy"],"prefix":"10.26508","volume":"9","author":[{"given":"Katia","family":"Corano Scheri","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/000e0be47","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, Feinberg School of Medicine, 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