{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:02:36Z","timestamp":1790740956501,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 EY 017313"],"award-info":[{"award-number":["R01 EY 017313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 EY 033516"],"award-info":[{"award-number":["R01 EY 033516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Thomas Foundation grant"},{"name":"Department of Ophthalmology, Wayne State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondrial dysfunction plays a major role in diabetic retinopathy development and in its resistance to halt after the reversal of hyperglycemia (metabolic memory). Diabetes also upregulates many long noncoding RNAs, RNAs with &gt;200 nucleotides with no reading frame, and several of them resist reversal after hyperglycemia cessation. Our aim was to investigate the role of LncRNA HOTAIR, a master regulator of chromatin dynamics, in mitochondrial biogenesis in diabetic retinopathy and in metabolic memory. Using retinal endothelial cells and M\u00fcller cells, incubated in high glucose (20 mM D-glucose), the effect of HOTAIR-siRNA on mitochondrial biogenesis was investigated by quantifying mitochondrial mass, copy numbers, and mtDNA replication, structure, and function. HOTAIR\u2019s role in metabolic memory was investigated by analyzing mitochondrial biogenesis in HOTAIR-siRNA transfected cells incubated in high glucose for four days, followed by normal glucose (5 mM D-glucose) for four days. HOTAIR was upregulated in both retinal vascular and nonvascular cells, and HOTAIR-siRNA ameliorated decreases in mtDNA biogenesis and protected their mitochondria from structural\/functional damage. Reversal of high glucose insult failed to ameliorate HOTAIR upregulation and impaired mtDNA biogenesis in both endothelial and M\u00fcller cells, but regulation of HOTAIR during high glucose incubation, which followed normal glucose, prevented a decrease in mitochondrial mass and mtDNA copies. Thus, HOTAIR has a major role in mitochondrial biogenesis and in the continued impaired biogenesis in both vascular and nonvascular cells. Regulating HOTAIR may provide a therapeutic option to inhibit the development\/progression of diabetic retinopathy.<\/jats:p>","DOI":"10.3390\/cells15040357","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:15:35Z","timestamp":1771334135000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of Mitochondrial Biogenesis in Diabetic Retinopathy"],"prefix":"10.3390","volume":"15","author":[{"given":"Jay","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, 4717 St. Antoine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-4942","authenticated-orcid":false,"given":"Renu A.","family":"Kowluru","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, 4717 St. Antoine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1056\/NEJMra021678","article-title":"Diabetic Retinopathy","volume":"350","author":"Frank","year":"2004","journal-title":"N. 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