Retinal degeneration in the mouse induced transplacentally by N-methyl-N-nitrosourea: Effects of constant illumination or total darkness

Abstract

The DNA alkylating agent, N-methyl-N-nitrosourea (MNU), when administered prenatally (on day 16 of gestation) provokes a progressive retinal degeneration in CD-1 albino mice reared in standard fluorescent lighting conditions (12 L: 12 D). This degeneration begins at about 4 weeks postnatally and worsens with age. To determine whether light was essential to the development of this lesion, animals in the present study were maintained in either constant light or constant darkness. Systematic measurement of the inner and outer segment lengths, the number of rows of photoreceptor cells and the thicknesses of the outer nuclear layer and whole retina were made to quantify degenerative changes in animals at 2-, 4-, 6-, 8-, 12-, and 16 weeks of age. The constant light caused a drastic reduction in thickness of the retinas of MNU-treated and control mice. The MNU-exposed animals reared in the dark did not demonstrate this reduction in retinal thickness, at least up to 16 weeks of age. Rather, measurements from this group were much like those for dark-reared control mice. The results of the present study suggest that the retinopathy induced by this dose of MNU may require secondary insults such as light, to amplify the lesions induced in utero by the drug.