RPE LACTATE TRANSPORTERS--A ROLE IN RETINAL SURVIVAL

视网膜色素上皮细胞（RPE）是视网膜色素上皮细胞（RPE）的外 视网膜。 它形成外部血-视网膜屏障，并调节 脉络膜血液之间的代谢物、离子和液体的运动 血管和神经视网膜。 特定的蛋白质调节屏障 和RPE的运输特性。 自从两个人的骚乱 阻挡层或载体功能可能对 在视网膜中，重要的是识别和表征蛋白质 来调节这些功能。 视网膜利用有氧糖酵解， 乳酸盐的浓度，无论是在光照下还是在黑暗中。 过量的乳酸是 通过RPE从视网膜下腔（SRS）运输到脉络膜。 乳酸穿过质膜的运动是由质子介导的， 偶联单羧酸转运蛋白（MCT）。 RPE细胞表达两种 单羧酸转运蛋白，MCT 1和MCT 3被极化到 RPE的顶膜和基底外侧膜。 而 MCT 1在许多组织中表达，MCT 3仅在RPE中检测到 细胞 调节SRS中的乳酸水平对于 维持周围基质的pH、渗透压和体积 感光细胞 我们的假设是， RPE顶膜和基底外侧膜中MCT的活性 调节乳酸盐和水从视网膜下流出 空间 可能的是，MCT 3表达或活性的变化将导致 随着时间的推移损害感光细胞的健康和功能。 这些研究的目标是描述时间和空间的特征， MCT 1和MCT 3在发育中的小鼠RPE中的表达。 我们将确定 MCT 3的表达是否在视网膜病变的动物中改变， 退化 这些研究的结果将提供新的和 关于RPE特异性转运蛋白作用的重要信息 调节乳酸盐和液体从视网膜下腔流出。 这些研究应该表明，MCT 3基因的缺陷是否可能导致 与视网膜色素上皮病变如黄斑变性有关。

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.