June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Plasma metabolomics of primary open-angle glaucoma in three prospective US cohorts and the UK Biobank
Author Affiliations & Notes
  • Oana Alina Zeleznik
    Channing Division of Network Medicine, Brigham and Women’s Hospital/Harvard Medical School, Massachusetts, United States
  • Jae Kang
    Channing Division of Network Medicine, Brigham and Women’s Hospital/Harvard Medical School, Massachusetts, United States
  • Jessica A Lasky-Su
    Channing Division of Network Medicine, Brigham and Women’s Hospital/Harvard Medical School, Massachusetts, United States
  • Clary B Clish
    Broad Institute of Massachusetts Institute of Technology and Harvard, Massachusetts, United States
  • Bernard Rosner
    Channing Division of Network Medicine, Brigham and Women’s Hospital/Harvard Medical School, Massachusetts, United States
  • Tobias Elze
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Anthony Khawaja
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Janey L Wiggs
    Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Louis R Pasquale
    Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Footnotes
    Commercial Relationships   Oana Zeleznik None; Jae Kang None; Jessica Lasky-Su None; Clary Clish None; Bernard Rosner None; Tobias Elze Genentech Inc, Code F (Financial Support); Anthony Khawaja None; Janey Wiggs None; Louis Pasquale Eyenovia, Skye Bioscience, Twenty Twenty, Code C (Consultant/Contractor)
  • Footnotes
    Support  NIH/NEI R01 EY015473
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2263. doi:
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    • Get Citation

      Oana Alina Zeleznik, Jae Kang, Jessica A Lasky-Su, Clary B Clish, Bernard Rosner, Tobias Elze, Anthony Khawaja, Janey L Wiggs, Louis R Pasquale; Plasma metabolomics of primary open-angle glaucoma in three prospective US cohorts and the UK Biobank. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2263.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To identify plasma metabolites associated with primary open-angle glaucoma (POAG) risk.

Methods : In a case-control study from the Nurses’ Health Study (NHS), NHSII and Health Professionals Follow-Up Study (HPFS), 602 incident POAG cases were 1:1 matched to 602 controls. LC-MS/MS metabolomics were measured on plasma samples; 367 metabolites passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 167 NMR metabolites were measured in serum samples from 2238 prevalent glaucoma cases and 44723 controls. Multiple logistic regression was used to identify metabolites associated with POAG in NHS/NHSII/HPFS and glaucoma in UK Biobank. In NHS/NHSII/HPFS, we also used Metabolite Set Enrichment Analysis to identify metabolite classes associated with POAG. All analyses adjusted for established glaucoma risk factors and relevant co-morbidities. False discovery rate (FDR) was used to adjust for multiple comparisons.

Results : Eight metabolite classes were associated (FDR<0.05) with POAG in NHS/NHSII/HPFS: triglycerides (TGs), diglycerides, two lysophospholipids classes [lysophosphatidylcholines and lysophosphatidylethanolamines], and one phospholipid class [phosphatidylethanolamines] were positively associated, while cholesteryl esters, carnitines, and organic acids and derivatives were inversely associated with POAG risk. Interestingly, polyunsaturated TGs with long fatty acyl chains were associated with a lower POAG risk while less unsaturated TGs with shorter fatty acyl chains were positively associated with POAG risk (Figure 1). In the UK Biobank, TGs and phospholipids (from which lysophospholipids are derived through hydrolysis), were positively associated with glaucoma, as found in NHS/NHSII/HPFS. Tyrosine, glucose, and glutamine were positively associated while acetate, 3-hydroxybutyrate, citrate, pyruvate and lactate were inversely associated with glaucoma (FDR<0.2).

Conclusions :
Higher levels of TGs, with potential differences by saturation and fatty acyl chain length, and phospholipids were adversely associated with POAG in both the NHS/NHSII/HPFS and the UK Biobank, suggesting that they play an important and complex role in POAG and may represent new screening and treatment targets.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1: Triglyceride (TG) associations with POAG risk by saturation (number of double bonds) and fatty acyl chain length (number of Carbon atoms) in NHS/NHSII/HPFS.

Figure 1: Triglyceride (TG) associations with POAG risk by saturation (number of double bonds) and fatty acyl chain length (number of Carbon atoms) in NHS/NHSII/HPFS.

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