INCREASE IN RETINYL PALMITATE CONCENTRATION IN EYES AND LIVERS AND THE CONCENTRATION OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN IN EYESOF VITILIGO MUTANT MICE

Retinyl esters play an important role in the visual cycle because they are involved in regeneration of 11-cis-retinal for use in rhodopsin f ormation. In the present study, retinyl ester concentrations were sign ificantly elevated in eyes and livers of mice homozygous for the vitil igo mutation (mi(vit)/mi(vit)). Vitiligo mice demonstrate a slowly pro gressing retinal degeneration characterized by gradual loss of photore ceptor cells and rhodopsin as well as uneven pigmentation of the retin al pigment epithelium (RPE). Analysis of retinoids by h.p.l.c. indicat ed that the retinyl palmitate level was increased fivefold in eyes of affected mice at 10 weeks postnatally and was threefold higher at 22 w eeks of age. Accumulation of retinyl palmitate occurred in the RPE rat her than the neural retina. Furthermore, the concentration of all-tran s-retinol was elevated in the RPE of vitiligo mice. Levels of interpho toreceptor retinoid binding protein (IRBP) were increased in vitiligo mice between ages 4 and 14 weeks, but returned to normal by 16 weeks. Increased IRBP levels were not due to increased protein synthesis beca use IRBP mRNA levels did not differ significantly between control and affected animals. To examine possible systemic involvement in vitiligo mice, retinoids were evaluated in liver and plasma. Mean hepatic tota l vitamin A levels in affected mice were approximately 1.7 times highe r than controls. Analysis of esterified and non-esterified retinoids i n liver showed that the concentration of retinyl palmitate was elevate d. Plasma retinol levels were normal. This study provides the first ev idence of altered systemic retinoid metabolism in vitiligo mice, which occurs, significantly, under normal dietary conditions.