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Metabolic changes associated with macular telangiectasia of retinal neurodegeneration
Marcus Fruttiger 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Macular Telangiectasia type 2 (MacTel) is an uncommon eye disease that can lead to blindness in the center of vision. Histologically, it is characterized by neural degeneration in the macula, specifically a loss of Müller glia cells, associated by vascular changes and photoreceptor degeneration, which are likely secondary to the glial changes. Genetically, the disease is complex, although a genome wide association study (GWAS) has identified variants in genes associated with the glycine-serine metabolism as the most important genetic risk factors. Serum analysis of MacTel patients has shown systemic low levels of glycine and serine, but pathology only occurs in the retina and patients are otherwise healthy. The glycine-serine metabolism is linked to numerous other pathway and global metabolomics serum analysis revealed changes in several adjacent pathways, implicating potential stress in the one-carbon, transmethylation and glutathione metabolism. Further changes were also found in several lipid groups, including the sphingolipid metabolism, where low serine levels can lead to the formation of deoxysphingolipids, which can contribute to MacTel pathology as they are known for their cytotoxic properties. These findings now facilitate a platform to investigate the molecular disease mechanisms of MacTel in animal models in future studies.
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