Differential recovery of retinal function after mitochondrial inhibition by methanol intoxication

PURPOSE. The authors' laboratory has previously documented formate-induced retinal toxicity in a rodent model of methanol intoxication. These studies determined functional, bioenergetic, and structural recovery of the retina after methanol intoxication. METHODS. Rats were intoxicated with methanol, and retinal function was asse ssed by electroretinography 72 hours after the initial dose of methanol and after a 72-hour recovery period. Retinal energy metabolites, glutathione ( GSH) concentrations, and histology were determined at the same time points. RESULTS. Both rod-dominated and UV-cone-mediated electroretinogram response s were profoundly attenuated in methanol-intoxicated rats. In rats allowed to recover from methanol intoxication, there was significant, although inco mplete, recovery of rod-dominated retinal function. However, there was no d emonstrable improvement in W-cone-mediated responses. Retinal adenosine tri phosphate (ATP), adenosine diphosphate (ADP), and GSH concentrations were s ignificantly reduced after intoxication. Although retinal energy metabolite s returned to control values after the recovery period, retinal GSH remaine d significantly depleted. Histopathologic changes were apparent in the phot oreceptors after methanol intoxication, with evidence of inner segment swel ling and mitochondrial disruption. In animals allowed to recover from metha nol intoxication, there was no evidence of histopathology at the light micr oscopic level; however, ultrastructural studies revealed subtle photorecept or mitochondrial alterations. CONCLUSIONS. These findings support the hypothesis that for mate inhibits r etinal mitochondrial function and increases oxidative stress. They also pro vide evidence for a differential sensitivity of photoreceptors to the cytot oxic actions of formic acid, with a partial recovery of rod-dominated respo nses and no recovery of UV-cone-mediated responses.