Methanol-induced visual toxicity in the rat

Abstract

Human methanol poisoning is characterized by formic acidemia, metabolic acidosis and blindness or serious visual impairment. Nonprimate species are ordinarily resistant to the accumulation of formate and the associated metabolic and visual toxicity. A nonprimate model of methanol-induced visual toxicity was developed using rats treated with subanesthetic concentrations of nitrous oxide to inhibit the oxidation of methanol's toxic metabolite, formic acid. Methanol-intoxicated rats developed formic acidemia, metabolic acidosis and visual toxicity within 36 hr of methanol administration analogous to the human methanol poisoning syndrome. Visual dysfunction was measured as reductions in the flash-evoked cortical potential and electroretinogram, which occurred coincident with blood formate accumulation. Alterations in the electroretinogram occurred at formate concentrations lower than those associated with other visual changes and provide functional evidence of direct retinal toxicity in methanol poisoning.