The monocarboxylate transport inhibitor, alpha-cyano-4-hydroxycinnamate, has no effect on retinal ischemia

Glial-derived monocarboxylate lactate is thought to be an important energy source for neurons during brain activation or in hypoxia-ischemia. Treatment with alpha-cyano-4-hydroxycinnamate (4-CIN), a monocarboxylate transporter inhibitor, has been recently reported to exacerbate delayed neuronal damage in a rat model of cerebral ischemia, an effect ascribed to inhibition of lactate/pyruvate transport. Since monocarboxylate transporters are abundant in the retina, we examined the effect of 4-CIN administration on the outcome of high intraocular pressure-induced retinal ischemia in rats. Retinal ischemic damage was assessed by changes in the electroretinogram (ERG), the retinal localization of choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS) immunoreactivities, and the loss of retinal mRNA for Thy-1. Intraperitoneal or intravitreal administration of 4-CIN had no effect on the ERG or the localization of ChAT and nNOS immunoreactivities in either the control retina or a retina subjected to ischemia/reperfusion. In addition, intravitreal injection of 4-CIN had no effect on ischemia-induced reduction of retinal mRNA levels for Thy-1. These results provide no evidence to support the view that blockade of lactate uptake and/or pyruvate entry into mitochondria for oxidative metabolism has an influence on the outcome of retinal ischemia/reperfusion.