Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus

PURPOSE: Inducible nitric oxide synthase has been implicated in the pathoge nesis of cerebral ischemic damage, in the angiogenic process and in diabeti c vascular damage. This study was undertaken to determine whether inducible nitric oxide synthase is present in the retinas from human subjects with d iabetes mellitus. METHODS: This was an experimental immunohistochemical prospective study. Te n postmortem eyes from five subjects with diabetes mellitus, 10 eyes from f ive subjects without diabetes and without known ocular disease, and two eye s from one subject with unilateral ocular ischemic syndrome secondary to se vere carotid artery obstruction were examined. We used immunohistochemical techniques and antibodies directed against inducible nitric oxide synthase, glial fibrillary acidic protein, and vimentin. The main outcome measure wa s immunoreactivity for these antibodies. RESULTS: Immunoreactivity for inducible nitric oxide synthase was not obser ved in retinas from all subjects without diabetes and without ocular diseas e. Six retinas from three subjects with diabetes and nonproliferative retin opathy, and the retina from the eye with ocular ischemic syndrome showed im munoreactivity for inducible nitric oxide synthase in cells with elongated processes. Based on morphology and on glial fibrillary acidic protein and v imentin immunoreactivity, this inducible nitric oxide synthase immunoreacti vity appeared to localize to retinal Muller glial cells. CONCLUSIONS: These observations suggest that Muller cells may be involved i n the microvascular remodeling of the diseased retina and that high concent rations of nitric oxide produced by inducible nitric oxide synthase could c ontribute to neurotoxicity and angiogenesis that occur in diabetic retinopa thy. (C) 2001 by Elsevier Science Inc. All rights reserved.