RPE LACTATE TRANSPORTERS--A ROLE IN RETINAL SURVIVAL

Thomas Jefferson University, Philadelphia PA

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Abstract

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.