Effects of the antioxidant butylated hydroxytoluene (BHT) on retinal degeneration induced transplacentally by a single low dosage of n‐methyl‐N‐nitrosourea (MNU)

A 1 mg/kg dose of the DNA alkylating agent, N‐methyl‐N‐nitrosourea (MNU), when administered on day 16 of gestation provokes a progressive retinal degeneration in CD‐1 albino mice reared under standard fluorescent lighting conditions (12 hr light : 12 hr dark); this degeneration begins at about 4 weeks post‐natally and worsens with age. It is accelerated by constant fluorescent light exposure but is retarded greatly by constant darkness, suggesting the importance of secondary insults in the post‐natal period for development of the degenerative disease. To determine whether the secondary photochemical damage might be specifically blocked, MNU‐exposed and control animals in the present study were fed an antioxidant‐enriched diet of Purina mouse chow supplemented with 0.75% butylated hydroxytoluene (BHT). A second group of MNU‐exposed and control animals were fed a non‐BHT supplemented standard Purina mouse chow diet. Systematic measurements of the number of rows of photoreceptor cell nuclei, the thickness of the inner/outer segment layer, and the thickness of the whole retina were made, to quantify any degenerative changes in animals 2, 4, 6, and 8 weeks of age. By 8 weeks, retinas of BHT‐fed, MNU‐exposed animals were significantly thicker and had more rows of photoreceptor cell nuclei than regular‐diet, MNU‐exposed animals. Moreover, the retinas of BHT‐fed animals, both for MNU‐exposed and controls, demonstrated sporadic morphologic changes in the form of circular configurations composed of ganglion cells, arcades of nuclear and plexiform layers, and, in one control animal, a hyperplastic nodule. These experiments suggested that MNU‐induced retinal degeneration may be retarded by a BHT‐enriched diet; however, continuous high doses of this compound pre‐ and post‐natally may induce other retinal abnormalities.