RPE LACTATE TRANSPORTERS--A ROLE IN RETINAL SURVIVAL

视网膜色素上皮(RPE)是外视网膜的守门人 视网膜。它形成外部的血-视网膜屏障，并调节 代谢物、离子和液体在脉络膜血液之间的运动 血管和神经视网膜。特定的蛋白质调节屏障 和RPE的传输特性。由于任何一个人的干扰 阻挡层或载体功能可能对 视网膜，识别和表征这些蛋白质是很重要的 来协调这些功能。 视网膜使用有氧糖酵解，并产生大量的 乳酸盐的含量，无论是在光明中还是黑暗中。过量的乳酸盐是 由视网膜色素上皮(RPE)从视网膜下间隙(SRS)输送到脉络膜。 乳酸通过质膜的移动是由质子介导的。 偶联单羧酸转运蛋白(MCTs)。RPE细胞表达两种 单羧酸转运体，MCT1和MCT3，极化到 RPE的顶膜和基侧膜。而当 MCT1在许多组织中表达，MCT3仅在RPE中检测到 细胞。调节SRS中的乳酸水平对于 保持基质周围的pH、渗透压和体积 感光细胞。我们的假设是，它是协调的 视网膜色素上皮根尖和基底外侧膜中单核细胞的活性 它调节乳酸和水从视网膜下流出 太空。MCT3表达或活性的变化很可能会 随着时间的推移，光感受器细胞的健康和功能会受到损害。 这些研究的目标是刻画时间和空间 MCT1和MCT3在小鼠视网膜色素上皮发育过程中的表达我们将决定 视网膜病变动物MCT3的表达是否发生改变 堕落的人。这些研究的结果将提供新的和 有关RPE特异性转运蛋白作用的重要信息 调节乳酸和液体从视网膜下腔流出。 这些研究应该表明MCT3基因中的缺陷是否可能是 与黄斑变性等RPE病理有关。

The retinal pigment epithelium (RPE) is the gatekeeper of the outer retina. It forms the outer blood-retinal barrier and regulates the movements of metabolites, ions, and fluid between the choroidal blood vessels and the neural retina. Specific proteins regulate the barrier and transport properties of the RPE. Since the disturbance of either the barrier or the carrier functions could have deleterious effects on the retina, it is important to identify and characterize the proteins that mediate these functions. The retina uses aerobic glycolysis and produces substantial quantities of lactate, both in the light and in the dark. Excess lactate is transported out of the subretinal space (SRS) to the choroid by the RPE. The movement of lactate across plasma membranes is mediated by proton- coupled monocarboxylate transporters (MCTs). The RPE cells express two monocarboxylate transporters, MCT1 and MCT3 that are polarized to the apical and the basolateral membranes of the RPE, respectively. While MCT1 is expressed in many tissues MCT3 has been detected only in RPE cells. Regulating lactate levels in the SRS is essential for maintaining the pH, osmolarity, and volume in the matrix surrounding photoreceptor cells. It is our hypothesis that it is the coordinated activity of the MCTs in the apical and basolateral membrane of the RPE that regulates the movement of lactate and water out of the subretinal space. It is likely that changes in MCT3 expression or activity would over time compromise the health and function of photoreceptor cells. The goals of these studies are to characterize the temporal and spatial expression of MCT1 and MCT3 in developing mouse RPE. We will determine whether the expression of MCT3 is altered in animals with retinal degenerations. The results of these studies will provide new and important information regarding the role of RPE specific transporters in regulating lactate and fluid movement out of the subretinal space. These studies should indicate whether defects in the MCT3 gene could be linked to RPE pathologies such as macular degeneration.