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Because lower and safer doses of aspirin could be used if its beneficial effects on retinopathy were due to antithrombotic effects, we compared the effects of a selective antiplatelet drug (clopidogrel) to those of aspirin in streptozotocin-induced diabetic rats. Clopidogrel did not prevent neuronal apoptosis, glial reactivity, capillary cell apoptosis, or acellular capillaries in the retina of diabetic rats. Aspirin, at doses yielding serum levels (&amp;lt;0.6 mmol\/l) well below the anti-inflammatory range for humans, prevented apoptosis of capillary cells and the development of acellular capillaries but did not prevent neuroglial abnormalities. The aldose reductase inhibitor sorbinil, used as the benchmark for the effect of the other drugs, prevented all abnormalities. The diabetic rat retina showed increased expression of the transcription factor CCAAT\/enhancer-binding protein-\u03b2, one of the known targets of low-intermediate concentrations of aspirin. Thus we found a spectrum of drug efficacy on the prevention of experimental diabetic retinopathy, ranging from the absent effect of a selective antiplatelet drug to the prevention of all abnormalities by an aldose reductase inhibitor. Aspirin at low-intermediate concentrations selectively prevented microangiopathy. The minimal effective dose of aspirin should now be sought.<\/jats:p>","DOI":"10.2337\/diabetes.54.12.3418","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"3418-3426","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":50,"title":["Aspirin at Low-Intermediate Concentrations Protects Retinal Vessels in Experimental Diabetic Retinopathy Through Non\u2013Platelet-Mediated Effects"],"prefix":"10.2337","volume":"54","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Gerhardinger","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeina","family":"Dagher","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Hoehn","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Lorenzi","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031209134911700_R1","doi-asserted-by":"crossref","unstructured":"The Early Treatment Diabetic Retinopathy Study Research Group: Effects of aspirin treatment on diabetic retinopathy: ETDRS report number 8. 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