Metabolic Regulation by Mechanistic Target of Rapamycin in the Retinal Pigment Epithelium

Project Summary

The retinal pigment epithelium (RPE) is a layer of cells next to the retina that are metabolically coupled to the retina’s photoreceptor neurons.  In age-related macular degeneration (AMD), functional interactions between the two types of cells are disturbed, which will result in both defects in energy metabolism and inefficient removal of metabolic intermediates in the outer retina.  Limited information is available for metabolic profiles of eye tissues, and the mechanistic links between RPE metabolomics and retinal degeneration are yet to be determined.

Mechanistic target of rapamycin (mTOR) is a key regulatory protein that controls the balance between cellular anabolism and catabolism.  We recently found that abnormally high activity of mTOR leads to degeneration of the RPE and retina.  The current project will use high-resolution mass spectrometry-based metabolomics approaches to measure temporal and spatial changes of metabolic pathways in the RPE and retina under both physiological and disease conditions, with a focus on mTOR-mediated signal transduction pathways.  The findings from our proposed studies will further define how the RPE supports the photoreceptor functions via metabolic coupling, and hopefully identify novel druggable targets for preventing RPE and retinal degeneration during AMD.