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.

Public Health Relevance

Patients with Usher syndrome type 1B frequently suffer from fluid accumulation in the retina (cystoid macular edema, or CME), which impairs central vision in young patients. The proposed research will explore why mutant MYO7A, the genetic cause of Usher 1B, affects water flow across the retinal pigment epithelium (RPE). It will also test the efficacy of the drugs, commonly prescribed for CME, on promoting water flow across Usher 1B RPE, thus potentially identifying the most suitable pharmacological treatment for CME in Usher 1B.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY031109-01
Application #
9886098
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Neuhold, Lisa
Project Start
2020-01-01
Project End
2021-12-31
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095