ERG ABNORMALITIES IN RELATION TO HISTOPATHOLOGIC FINDINGS IN VITILIGOMUTANT MICE

The vitiligo, mi(vit), mutation has several prenatal and perinatal eff ects on development of the retinal pigment epithelium, and later, lead s to extensive, progressive degeneration of photoreceptor cells in the neural retina of homozygous affected mice. The aim of the present stu dy was to determine by functional criteria how early can abnormalities be detected in the neural retina. Electroretinograms (ERGs) were corr elated with histopathological findings in the same animals, Congenic h omozygous mutants, heterozygotes, and homozygous wild-type mice were s tudied at 2, 3, 6, 24 and 56 weeks of age, the same animals being test ed serially at the three older time points. The nontested eye of each animal was embedded in Epon and sectioned at 1 mu m for light microsco pic study. ERG recordings from vitiligo homozygotes differed from hete rozygous and wild-type mice, but the latter two groups did not differ from each other. As early as two weeks of age, homozygous mutants show ed a significant reduction of rod dominated maximum ERG a-wave and b-w ave amplitude. ERG b-wave sensitivity (sigma) was significantly reduce d. and ERG implicit times were delayed for homozygous mutants at 3 (a- wave) and 6 (b-wave) weeks of age. This is the first study to report r educed and delayed ERG a-waves and b-waves in this animal model, like the early functional abnormalities in human retinitis pigmentosa, and also the first to show short and disoriented rod outer segments, begin ning retinal separation from the pigment epithelium, and a few macroph age-like cells already present in the subretinal space at 2 weeks of a ge (in three of four homozygous mutant eyes examined). Given these ear ly functional and structural abnormalities in the neural retina, it re mains to be determined whether the mi gene targets the retinal pigment epithelial cell, the photoreceptor cell, or both. (C) 1997 Academic P ress Limited.