Parafoveal Macular Telangectasia studies on VLDLR mice

MacTel is a disease of unknown origin that causes retinal degeneration and macular vessel growth. We will study the VLDLR KO mouse with these two characteristics as a model. We have found that VLDLR loss causes decreased glucose uptake regulated by glut 1 which is suppressed by upregulation of GPR40, a lipid sensor upregulated by decreased lipid uptake in cells. We will study mitochondrial regulation of photoreceptor degeneration and production of VEGF causing macular vascular lesions.

As Sjogren Larsson Syndrome (known gene defect in a fatty acid aldehyde dehydrogenase ALDH3A2) has a similar but exaggerated MacTel phenotype with very early onset including macular “crystals” lack of macular pigment a buildup of macular pigment at the margin of the “MacTel” area “cysts” or areas of hypo-reflectivity seen on OCT in the central macular area Muller cell involvement (although as we know this is non specific)

I propose a metabolomics analysis on fibroblasts of SLS, MacTel and matched control patients. A comparison of lipidomic profile, (alpha, beta and other fatty acid oxidation) Krebs cycle analysis, OX PHOS and glycolysis. Fibroblasts are commonly used for lipid analysis for diabetes and lipid disorders (J. Lipid Res.2012. 53: 1012–1020.) There is a literature on lipid abnormalities in SLS fibroblasts.