{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:27:46Z","timestamp":1787254066555,"version":"build-2736575974"},"reference-count":48,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"NIH","award":["1R21EY036537-01 (MA)"],"award-info":[{"award-number":["1R21EY036537-01 (MA)"]}]},{"name":"NIH","award":["P30EY004068 (AI)"],"award-info":[{"award-number":["P30EY004068 (AI)"]}]},{"name":"NIH","award":["R01 EY030054 (MA)"],"award-info":[{"award-number":["R01 EY030054 (MA)"]}]},{"name":"NIH","award":["R01EY023315 (MA)"],"award-info":[{"award-number":["R01EY023315 (MA)"]}]},{"name":"NIH","award":["R01EY034964 (AI)"],"award-info":[{"award-number":["R01EY034964 (AI)"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetic\u00a0retinopathy (DR) remains a leading cause of blindness, characterized by progressive neurovascular dysfunction. While the enzyme 12\/15-lipoxygenase (12\/15-LO) and its metabolites are upregulated in DR, their interactions with epigenetic regulators, such as miRNAs, are poorly understood. This study investigates the role of 12\/15-LO in miRNA dysregulation and its functional consequences in a type 1 diabetic mouse model. We generated 12\/15-LO knockout mice on an (Ins2+\/akita) (Akita) background. Retinal miRNA expression was profiled using microarray analysis, and retinal structure and function were assessed using histology and electroretinography. Our results demonstrate that diabetes induces significant dysregulation of a distinct subset of retinal miRNAs (e.g., downregulation of miR-329-3p and miR-431-5p and upregulation of miR-3078-3p and miR-323-5p). Deletion of 12\/15-LO normalized a subset of these diabetes-associated miRNA alterations and prevented retinal thinning and the loss of neuronal markers (NeuN and SCGN). Functionally, 12\/15-LO deletion rescued diabetes-induced deficits in retinal ganglion cell (positive scotopic threshold response), cone bipolar cell (photopic b-wave), and cone pathway function (response to natural noise). In conclusion, our findings establish 12\/15-LO as a critical upstream regulator of miRNA in the diabetic retina and demonstrate that its deletion protects against neuronal damage in DR. Thus, targeting the 12\/15-LO pathway may represent a novel therapeutic strategy to mitigate neuronal dysfunction associated with DR progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Retina of Akita diabetic mice demonstrated significant thinning and dysfunction. Deletion of 12\/15-lipoxygenase (12\/15-LO) in Akita diabetic mice, an essential enzyme that metabolizes arachidonic acid to 12- and 15-hydroxyeicosatetraenoic acids, restored normal retinal thickness and preserved retinal neurons and function. Deletion of 12\/15-LO selectively restored essential mature forms of miRNA, such as miR431 and miR329, which are implicated in neuroprotection, synaptic plasticity, and cellular response to stress. Targeting 12\/15-LO and its metabolites has the potential to protect retina against diabetes neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0179","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:31:57Z","timestamp":1784827917000},"page":"1673-1684","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of 12\/15-Lipoxygenase Preserves Retinal Thickness and Function and Selectively Restores Dysregulated miRNAs in Experimental Diabetes Mice"],"prefix":"10.2337","volume":"75","author":[{"given":"Mohamed","family":"Moustafa","sequence":"first","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youstina","family":"Guirguis","sequence":"additional","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Humble","sequence":"additional","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martena","family":"Grace","sequence":"additional","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"},{"name":"Ross University School of Medicine 3 , Miramar, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jianghan University 4 , Wuhan City, Hubei Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N.","family":"Ensley","sequence":"additional","affiliation":[{"name":"Mercer University School of Medicine 5 , Macon, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Risner","sequence":"additional","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"},{"name":"Foundational Medical Studies, Oakland University William Beaumont School of Medicine 6 , Rochester, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Saul","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University 7 , Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8480-6252","authenticated-orcid":false,"given":"Ahmed S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Visual, and Anatomical Sciences and Pharmacology, Wayne State University School of Medicine 8 , Detroit, MI"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University 9 , Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-7972","authenticated-orcid":false,"given":"Mohamed","family":"Al-Shabrawey","sequence":"additional","affiliation":[{"name":"Eye Research Center, Oakland University William Beaumont School of Medicine 1 , Rochester, MI"},{"name":"Eye Research Institute, Oakland University 2 , Rochester, MI"},{"name":"Foundational Medical Studies, Oakland University William Beaumont School of Medicine 6 , Rochester, 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