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Editors Selection IGR 10-3

Basic Science: POAG and Plasma Metabolites

Subhabrata Chakrabarti

Comment by Subhabrata Chakrabarti on:

Glaucoma is a complex disease with a multifactorial etiology and primary open-angle glaucoma (POAG) is the commonest form. Various multi-omic approaches have been employed to dissect the molecular mechanisms underlying POAG. Large scale genomic studies have revealed chromosomal loci and associated gene variants that suggests the involvement of metabolic pathways involved in physiological maintenance of the optic nerve.1

Metabolomics involves characterizations of metabolites from various body fluids and tissues and provides valuable insights into disease pathogenesis and progression.2 In the present study, Zeleznik and colleagues identified potential metabolites that may be susceptible to POAG. Metabolite profiling revealed higher levels of diglycerides and triglycerides that were adversely associated with incident POAG cases across all the health cohorts and were also replicated in a cross-sectional UK biobank cohort. Further, the previously observed associations of phospholipids and organic acids and mitochondrial dysfunctions in POAG were also seen in the present cohort.3-6 Additionally, there was a stronger association of POAG with paracentral visual-field loss.

Further, the previously observed associations of phospholipids and organic acids and mitochondrial dysfunctions in POAG were also seen in the present cohort
The strength of the present study lies in its robust study design comprising incident cases of POAG and matched controls from three health cohorts sampled at least ten years ahead of developing the disease. The measured metabolites were relatively stable and the data was analyzed under five different models adjusting for various covariates. Previous studies that documented metabolomic profiles of POAG patients were limited by the vagaries of small sample size, treatment biases and inappropriate choice of controls.3-6 The variability of the circulating metabolites prescribes sampling at uniform time points using appropriate screening platforms to ensure data homogeneity.2

The limitations pertaining to the generalizability of the results globally (as the data was predominantly Caucasian) and different screening technologies notwithstanding, the present study provides meaningful insights into POAG pathogenesis that warrants further functional validations.

References

  1. Gharahkhani P, et al. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat Commun. 2021;12:1258.
  2. Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 2004;22:245-252.
  3. Wang Y, Hou XW, Liang G, Pan CW. Metabolomics in glaucoma: a systematic review. Invest Ophthalmol Vis Sci. 2021;62:9.
  4. Leruez S, et al. A metabolomics profiling of glaucoma points to mitochondrial dysfunction, senescence, and polyamines deficiency. Invest Ophthalmol Vis Sci. 2018;59:4355-4361.
  5. Myer C. et al. Differentiation of soluble aqueous humor metabolites in primary open-angle glaucoma and controls. Exp Eye Res. 2020;194:108024.
  6. Tang Y, et al. Metabolomic profiling of aqueous humor and plasma in primary open-angle glaucoma patients points towards novel diagnostic and therapeutic strategy. Front Pharmacol. 2021;12:621146.

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