Dr. Metallo is exploring the role of metabolic dysregulation in MacTel. Genetics and metabolomics studies have indicated that some MacTel patients have decreased levels of the amino acids serine and glycine in plasma. More recent genetics studies have identified patients with genetic defects in sphingolipid metabolism. Dr. Metallo’s laboratory is now quantifying amino acid and sphingolipid abundances in the blood of healthy patients and those with MacTel to determine how each metabolite is altered. They also perform targeted studies to measure serine and sphingolipid metabolism in cultured retinal pigment epithelial (RPE) cells and mice. Specifically, they administer stable isotope labeled nutrients and use mass spectrometry to quantify isotope enrichment to trace the activity of these metabolic pathways. Finally, they are working to characterize how dietary manipulation of amino acids impacts retinal sphingolipids and visual phenotypes in mice. These studies will provide mechanistic insights into how dysfunctional metabolic pathways drive MacTel. Ultimately, this information will enable LMRI identify new therapeutic approaches to treat this disease.
