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These three drugs differ in their ability to inhibit cyclooxygenase but share an ability to inhibit nuclear factor-\u03baB (NF-\u03baB). Diabetes of 9\u201310 months duration significantly increased the number of TUNEL (transferase-mediated dUTP nick-end labeling)-positive capillary cells and acellular (degenerate) capillaries in the retinal vasculature, and all three salicylate-based drugs inhibited this cell death and formation of acellular capillaries without altering the severity of hyperglycemia. In short-term diabetes (2\u20134 months), all three salicylates inhibited the diabetes-induced loss of neuronal cells from the ganglion cell layer. Oral aspirin (as a representative of the salicylate family) inhibited diabetes-induced increase in NF-\u03baB DNA-binding affinity in electrophoretic mobility shift assay and transcription factor array in nuclear extract isolated from whole retina. All three salicylates inhibited the diabetes-induced translocation of p50 (a subunit of NF-\u03baB) into nuclei of retinal vascular endothelial cells of the isolated retinal vasculature, as well as of p50 and p65 into nuclei of cells in the ganglion cell layer and inner nuclear layer on whole-retinal sections. Sulfasalazine (also as a representative of the salicylates) inhibited the diabetes-induced upregulation of several inflammatory gene products, which are regulated by NF-\u03baB, including vascular cell adhesion molecule, intracellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 in whole-retinal lysate. Salicylates, in doses administrated in our experiments, inhibited NF-\u03baB and perhaps other transcription factors in the retina, were well tolerated, and offered new tools to investigate and inhibit the development of diabetic retinopathy.<\/jats:p>","DOI":"10.2337\/db06-0789","type":"journal-article","created":{"date-parts":[[2007,1,26]],"date-time":"2007-01-26T20:11:02Z","timestamp":1169842262000},"page":"337-345","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":122,"title":["Salicylate-Based Anti-Inflammatory Drugs Inhibit the Early Lesion of Diabetic Retinopathy"],"prefix":"10.2337","volume":"56","author":[{"given":"Ling","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Medicine, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott J.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise A.","family":"Hatala","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy S.","family":"Kern","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University, Cleveland, Ohio"},{"name":"Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031208565543600_R1","doi-asserted-by":"crossref","unstructured":"Mizutani M, Kern TS, Lorenzi M: Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. 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