RETINAL DEGENERATION INDUCED BY N-METHYL-N-NITROSOUREA AND DETECTION OF 7-METHYLDEOXYGUANOSINE IN THE RAT RETINA

Retinal degeneration induced by a single parenteral dose (40 mg) of N- methyl-N-nitrosourea (MNU) was studied in rats and rabbits. Sequential observations showed that severe pathological changes, that is, comple te or widespread destruction of the photoreceptor layer and the outer nuclear layer of the retina, occurred in both animals by 72 hr after t he administration of MNU. At week 5, at the end stage of the retinal d egeneration induced by MNU, thin remnants remained with the inner nucl ear layer in direct contact with the pigment epithelium. An additional immunohistochemistry study using antibodies against 7-methyldeoxyguan osine (7-mdGua), revealed the presence of high levels of 7-mdGua DNA a dducts in the nuclei of the outer nuclear layer cells. This finding su ggests that the alkylation of the outer nuclear layer by MNU was the d irect cause of the retinal degeneration seen in these animals.