The eyes of 200 rats (Mol·SPRD, Moellegaard Ltd., Skensvet, Denmark), 8 weeks of age and of both sexes, were examined routinely with a photo-slitlamp microscope (Zeiss) and opthalmoscope (Heine) 3-4 times in the course of four different 12-week toxicity studies. The animals were kept under constant lighting conditions at a room temperature of 20 ± 2° C and 5 5 ± 5% humidity on a standard diet. More than 70% of the animals were found to have more or less prominent corneal opacities already at the beginning of the study. These were morphologically characterized as meshwork-like alterations of the deeper corneal epithelium, mostly located in the central and nasal region. The temporal, upper and lower periphery remained always unaffected. Male animals were more frequently and more intensively affected than the females. The occurrence of the opacity was totally independent of the treatment scheme (controls and drug dosages, respectively), showing a slight increase in density in some of the animals of all groups and remaining stable in others. Regression was rarely observed. Light and electron microscopical investigations demonstrated focal degenerations of the basal epithelial cell layer as well as alterations of its basement membrane. The lesion was not associated with inflammation or irritation. Therefore, we considered that a genetically determined metabolic disorder of the basal epithelial cells might have led to the impairment of basement membrane synthesis. Further screenings performed in conjunction with the breeder evidenced that these opacities are probably caused by a spontaneous mutation with a complex, not X-linked genetic background.

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