Targeting Metabolic Homeostasis in Dysfunctional CHM Retinal Pigment Epithelia
Awardee: Kathleen Boesze-Battaglia
Institution: University of Pennsylvania
Grant Amount: $61,760.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
Loss of vision due to choroideremia (CHM), a progressive retinal degenerative disease affects 1 in 50,000 males. Advanced imaging modalities have recently documented sub-clinical changes in the retinal pigment epithelia (RPE) of CHM patients. While metabolomic studies demonstrate dysfunctional metabolism in CHM patients characterized by a disruption of lipid homeostasis. Collectively, these observations implicate RPE-mediated metabolic dysregulation resulting from loss of Rab Escort Protein-1 (REP1) as an etiological factor in CHM. The Boesze-Battaglia lab has extensive experience with lipid homeostasis in models of human retinal degenerations. To explore the potential of metabolic pathways as therapeutic targets for CHM, we have analyzed induced pluripotent stem cell (iPSC)-derived retinal cell from CHM patients. Treatment strategies for CHM are limited albeit clinical trials for gene augmentation strategies are underway. The efficiency of such treatments may not be truly appreciated or fully assessed for nearly a decade due to the slow progressive nature of the disease. Therefore, there remains an unmet need to explore other options to preserve the health and integrity of the retina prior to noticeable degeneration of the eye. Our goal is to define metabolic imbalance in CHM RPE in an effort to restore metabolic homeostasis and RPE function using CHM-patient specific cell models.