The rat electroretinogram in combined zinc and vitamin A deficiency.

To assess the relative importance and interdependence of zinc and vitamin A in retinal function, a group of 36 male Wistar rats were raised in dim illumination and deprived of both zinc and vitamin A (Z-A-) for 90 days (Phase I) until they lost weight and showed signs of both vitamin A and zinc deficiency. Scotopic electroretinograms (ERGs) showed an average 1.5 log unit elevation in light intensity needed to elicit a 200 microV b-wave (criterion intensity) as compared to a control-pair-fed group of rats. Tissue samples from the Z-A- rats showed undetectable liver vitamin A (less than 10 micrograms/g) and a significantly decreased level of femur zinc compared to the control group (P = 0.02). There was photoreceptor outer segment degeneration and loss of cells in the outer nuclear layer of the retina. For Phase II the 24 surviving rats were randomized into three treatment groups--one group remained vitamin A-deficient (A-) but received zinc and retinoic acid, the second remained zinc-deficient (Z-) but received vitamin A and retinoic acid, and the third group was repleted with both zinc and vitamin A (Z+A+) and also received retinoic acid. ERGs were performed 30 and 60 days after randomization. The criterion intensity of the Z+A+ and Z- groups approached normal by 60 days, while that of the A- rats deteriorated a further 1.0 log unit. Histologic studies of the A- rats showed abnormalities in cornea, photoreceptor outer segments, and gut mucosa. All animals had testicular atrophy. Vitamin A repletion significantly reverses retinal degeneration from the Z-A- state even in the presence of moderate zinc deficiency. Zinc supplementation alone does not prevent ongoing retinal degeneration from severe vitamin A deficiency.