RETINOL TRANSPORT PROTEINS IN RETINAL PIGMENT EPITHELIUM

视黄醇(维生素A)及其衍生物作为视觉生色团发挥着重要作用。 在光传导中起着至关重要的作用。血浆视黄醇是从 肝到眼与两种血浆蛋白的复合体：血清转甲状腺素 和血清视黄醇结合蛋白(SRBP)。视网膜色素 上皮(RPE)隔离、酯化和储存视黄醇，以及 将其传输到感光器。这些过程可能是由 几种胞质和光感受器间类维甲酸结合蛋白。 然而，视黄醇转移到视网膜的确切模式是 正在积极调查的对象。最近我们发现，在 大鼠，RPE特异性地合成TTR和SRBP，这表明这些 两种视黄醇结合蛋白也可能参与眼内 视黄醇的运输。 我们现在建议进一步调查这些调查结果。我们想确定一下 在大鼠中，RPE是否是眼TTR和SRBP的唯一来源 蛋白质，RPE是否向视网膜分泌TTR和SRBP，以及 TTR和SRBP的表达存在明显的昼夜循环。我们将尝试 测定培养的人和大鼠RPE细胞是否合成和分泌 TTR和SRBP。我们检测到TTRmRNA水平在第一个月激增 在大鼠出生后一天，想要探索是否伴随着激增 在SRBP mRNA水平上发生，以及这种表达模式是否是 依赖光的过程。最后，我们将研究Ttr的表达。 以及RCS/RDY大鼠的SRBP，后者发展为遗传性视网膜 继发于RPE功能障碍的营养不良。 这些研究应提供有关眼部TTR和 SRBP合成，为视黄醇的潜在因素提供了新的见解 在眼睛中循环，并有助于了解色素 视网膜病变。

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.