Fig. 5.

Both NADPH oxidase and mitochondria in mouse retina contribute to diabetes-induced generation of superoxide. Apocynin (APO), an inhibitor of NADPH oxidase, was administered daily (i.p. injections at a dose of 36 mg/kg). Methylene blue (MB), which donates electrons directly to mitochondrial cytochrome oxidase and thereby bypasses the leaky electron transport system in diabetes, was administered daily in drinking water at a dose of 5 mg/day. Both therapies significantly inhibited the diabetes-induced generation of superoxide by the retina. Data are expressed as a percent of the value of N wild-type controls. Duration of diabetes was 2 mo at the time of this assay, and administration of both agents began 1 wk after the onset of diabetes (n = 5 mice per group, 4 mo of age when killed).