Dr. Mitra F. Tedrick from National Eye Institute Awarded $65,000 Knights Templar Eye Foundation Grant for Stargardt Disease Research

Dr. Mitra F. Tedrick from National Eye Institute, Bethesda, Maryland was awarded a $65,000 grant for the research entitled: Stem cell-based drug discovery platform targeting lipid handling defects in Stargardt Disease

Stargardt disease is a rare inherited retinal degeneration, affecting 1 in 10,000 children in the U.S., with no current treatment. Progressive photoreceptor (PR) cell death induced by atrophied retinal pigment epithelium (RPE) leads to vision loss in patients. The disease is primarily caused by mutations in gene ABCA4. Earlier stages of Stargardt disease are characterized by the accumulation of lipid-rich lipofuscin deposits in the RPE, suggesting a defect in lipid homeostasis in the eye. Substantial genetic heterogeneity caused by more than 800 mutations in ABCA4 is associated with the differences in severity of disease phenotype in individuals harboring these mutations. Recently, others and we have identifi ed ABCA4 on the apical surface of RPE cells, challenging the current dogma that ABCA4 is a PR-specific protein. The discovery of ABCA4 expression in RPE cells provides a new link to disease pathogenesis and the potential to discover a well-informed treatment. Dr. Tedrick has developed an in vitro model for Stargardt disease using ABCA4 mutant induced pluripotent stem cell (iPSC)-derived RPE. Compared to healthy iPSC-RPE, Stargardt iPSC-RPE demonstrates disease phenotype of lipid deposition and progressive RPE atrophy. Dr. Tedrick’s ability to recapitulate Stargardt disease phenotype in ABCA4 mutant iPSC-RPE without the use of Stargardt POS suggests a cell-autonomous lipid metabolism defect in these cells. Here Dr. Tedrick is proposing a high-throughput drug screening to discover drugs that can improve lipid metabolism and handling in RPE cells and ameliorate Stargardt disease phenotype in the iPSC-RPE model. In addition, Dr. Tedrick will validate their drug discovery candidate/s using Stargardt patient-RPE with different genotypes and phenotypic subtypes. Our experiments seek to find drugs that can improve lipid metabolism/handling in these cells but do not interfere with their normal functioning.