Exploring the relationship of water flow across the RPE and mutant-MYO7A/Usher 1B

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Project Summary The retinal pigment epithelium (RPE) has active transport mechanisms and epithelial junctions that regulate water flow from the apical to the basal surface of the cell. Defects in either of these aspects of RPE function may promote disorders, such as cystoid macular edema (CME), and subsequent visual impairment. Usher Syndrome type 1B (USH1B), which is caused by mutations in MYO7A, includes a relatively high incidence of CME. However, the mechanism of CME in USH1B is unclear. Here, we propose to explore the suggestion that MYO7A is required for normal fluid flow across the RPE. Using RPE cultures, differentiated from induced pluripotent stem cells (iPSCs), derived from USH1B patients, we will test this suggestion and investigate whether loss of MYO7A function results in defective localization of proteins involved in the RPE junctional complex or in transmembrane ion and water flow. Further, we will use these iPSC-RPE cultures to test the efficacy of currently-used medications for CME in increasing water flow across the RPE. These studies will potentially provide novel insight into the retinal function of MYO7A, and a better understanding of impaired vision in USH1B, particularly that resulting from CME.