Gene Regulation of RPE Maintenance

We will evaluate the role of the MYRF transcription factor, which controls the expression of other genes in the RPE,  in supporting RPE function and protecting against macular degeneration-relevant stresses.

For Aim 1, we will study the role of the MYRF transcription factor in maintaining retinal pigment epithelial (RPE) function. Using an inducible mouse model to delete this gene in the adult RPE, we will assess the histologic, electrophysiologic, structural, and gene expression effects on the RPE. For Aim 2, we will use knockdown and overexpression experiments in RPE culture models to assess the role of MYRF in key aspects of RPE cell structure and physiology. We will then evaluate the ability of MYRF to protect against RPE stresses relevant to age-related macular degeneration.

Our proposal is innovative in that we are looking at the role of a very highly expressed transcription factor that has a developmental role and remains highly expressed in the mature RPE. We will apply knowledge of developmental pathways and try to co-opt these to improve RPE function and response to stress.

This proposal will determine whether genes important in RPE development but remain very highly expressed in adulthood may represent a novel therapeutic approach for dry age-related macular degeneration and other disease of deteriorating RPE physiology. Through this work, we will define genes and pathways that support RPE function.