Systemic lipid dysregulation is a risk factor for macular neurodegenerative disease
Details
Publication Year 2020-07-22,Volume 10,Issue #1,Page 12165
Journal Title
Scientific Reports
Publication Type
Journal Article
Abstract
Macular Telangiectasia type 2 (MacTel) is an uncommon bilateral retinal disease, in which glial cell and photoreceptor degeneration leads to central vision loss. The causative disease mechanism is largely unknown, and no treatment is currently available. A previous study found variants in genes associated with glycine-serine metabolism (PSPH, PHGDH and CPS1) to be associated with MacTel, and showed low levels of glycine and serine in the serum of MacTel patients. Recently, a causative role of deoxysphingolipids in MacTel disease has been established. However, little is known about possible other metabolic dysregulation. Here we used a global metabolomics platform in a case-control study to comprehensively profile serum from 60 MacTel patients and 58 controls. Analysis of the data, using innovative computational approaches, revealed a detailed, disease-associated metabolic profile with broad changes in multiple metabolic pathways. This included alterations in the levels of several metabolites that are directly or indirectly linked to glycine-serine metabolism, further validating our previous genetic findings. We also found changes unrelated to PSPH, PHGDH and CPS1 activity. Most pronounced, levels of several lipid groups were altered, with increased phosphatidylethanolamines being the most affected lipid group. Assessing correlations between different metabolites across our samples revealed putative functional connections. Correlations between phosphatidylethanolamines and sphingomyelin, and glycine-serine and sphingomyelin, observed in controls, were reduced in MacTel patients, suggesting metabolic re-wiring of sphingomyelin metabolism in MacTel patients. Our findings provide novel insights into metabolic changes associated with MacTel and implicate altered lipid metabolism as a contributor to this retinal neurodegenerative disease.
Publisher
NPG
Research Division(s)
Population Health And Immunity
PubMed ID
32699277
Open Access at Publisher's Site
https://doi.org/10.1038/s41598-020-69164-y
NHMRC Grants
NHMRC/1102971NHMRC/1054618
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-08-05 10:22:53
Last Modified: 2020-08-05 11:07:56
An error has occurred. This application may no longer respond until reloaded. Reload 🗙