RETINOL TRANSPORT PROTEINS IN RETINAL PIGMENT EPITHELIUM

As the visual chromophore, retinol (vitamin A) and its derivatives play a vital role in phototransduction. Plasma retinol is transported, from the liver to the eye in complex with two plasma proteins: serum transthyretin (TTR) and serum retinol-binding protein (SRBP). The retinal pigment epithelium (RPE) sequesters, esterifies and stores retinol, and transports it to the photoreceptors. These processes may be mediated by several cytosolic and interphotoreceptor retinoid-binding proteins. However, the precise mode of retinol translocation to the retina is the subject of active investigation. Recently we discovered that, in the rat, the RPE specifically synthesizes TTR and SRBP, suggesting that these two retinol-binding proteins may also participate in intraocular transport of retinol. We now propose to pursue these findings further. We wish to ascertain whether, in the rat, the RPE is the sole source of ocular TTR and SRBP protein, whether the RPE secretes TTR and SRBP to the retina, and whether a diurnal cycle exists for TTR and SRBP expression. We shall attempt to determine whether cultured human and rat RPE cells synthesize and secrete TTR and SRBP. We have detected a surge in TTR mRNA levels on the first postnatal day in the rat, and wish to explore whether a concomitant surge occurs in SRBP mRNA levels, and whether this pattern of expression is a light-dependent process. Finally, we shall study the expression of TTR and SRBP in the RCS/rdy rat, which develops an inherited retinal dystrophy secondary to RPE dysfunction. These studies should furnish fundamental information on ocular TTR and SRBP synthesis, provide new insights into the factors underlying retinol cycling in the eye, and contribute to an understanding of the pigmentary retinopathies.