{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:32:56Z","timestamp":1768703576461,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,10,23]],"date-time":"2001-10-23T00:00:00Z","timestamp":1003795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increased vascular permeability could be involved in the pathogenesis of diabetic retinopathy. The present study was aimed at assessing whether high glucose concentrations can impair retinal endothelial cell barrier function directly, irrespective of changes in other determinants of permeability, and the role of non\u2010enzymatic glycation and polyol pathway activation in these alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bovine retinal endothelial cells (BREC) were exposed for various periods to high glucose vs iso\u2010osmolar mannitol and normal glucose containing media\u00b1agents mimicking or inhibiting advanced glycation end product (AGE) formation and polyol pathway activation. Monolayer permeability was assessed by measuring the transendothelial passage of <jats:sup>125<\/jats:sup>I\u2010labeled proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Permeability increased significantly (up to +70%) in BREC exposed to high glucose, but not to mannitol, for 1\u201330 days, vs normal glucose control cells. Exposure to AGE\u2010modified bovine serum albumin (BSA) (\u2a9690%) and, to a lesser extent, sorbitol (+28%) mimicked the high glucose effect. The AGE formation and nitric oxide synthase (NOS) inhibitor aminoguanidine significantly reduced (by 60%) changes induced by 30\u2010day exposure to high glucose, whereas methylguanidine, which inhibits only NOS activity, did not affect permeability. Aldose reductase or sorbitol dehydrogenase inhibitors decreased (by \u223c40%) the enhanced leakage produced by 1\u2010day, but not 30\u2010day, incubation in high glucose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present results indicate that high glucose is capable of impairing retinal endothelial cell barrier function directly and that non\u2010enzymatic glycation and polyol pathway activation may mediate these changes, with AGEs participating in the long\u2010term alterations and increased flux through the sorbitol pathway in the short\u2010term effect. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.227","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:27:19Z","timestamp":1030292839000},"page":"448-458","source":"Crossref","is-referenced-by-count":20,"title":["Increased retinal endothelial cell monolayer permeability induced by the diabetic milieu: role of advanced non\u2010enzymatic glycation and polyol pathway 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