Novel roles for the retinal pigment epithelium in expression and turnover of interphotoreceptor retinoid-binding protein

Vertebrate visual function relies on specific interactions between the neural retina and the retinal pigment epithelium (RPE). These interactions are mediated by the interphotoreceptor matrix (IPM). The molecular components of the IPM are actively produced and secreted by the retina and RPE.; The quantities of individual IPM components are carefully regulated, and abnormal expression of matrix constituents is associated with disease. Little is known about the mechanisms regulating the amount of any matrix constituent. The major soluble protein in the IPM is interphotoreceptor retinoid-binding protein (IRBP). IRBP facilitates the exchange of retinoids during the "visual cycle".; Since IRBP is both abundant and soluble within the IPM, it provides a unique opportunity to study the mechanisms regulating turnover of matrix constituents. Regulation of IRBP removal appears to be an important determinant of its concentration in the IPM. Two systems have been used here to evaluate the expression and turnover of IRBP. Zebrafish IRBP mRNA levels are under circadian regulation. Zebrafish have herein been used to examine the relationship between this circadian mRNA expression and the amount of IRBP in the IPM. Unlike the mRNA, IRBP levels remain constant throughout the light/dark cycle, and IRBP is rapidly removed from the IPM in either light or dark.; The Xenopus laevis system has been used to examine the rate of IRBP removal from the IPM and to address potential mechanisms of IRBP turnover. IRBP is rapidly removed from the Xenopus EPM, with a biological half-life of ∼10 hours. One potential mechanism for this rapid removal is uptake by the RPE. The RPE contains a surprisingly large proportion (20%) of the total IRBP in the eye, and uptake by the RPE occurs in conditions of either light or dark.