June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration
Author Affiliations & Notes
  • Janice Kim
    Transitional Year Program, Sky Ridge Medical Center, Lone Tree, Colorado, United States
    Harvard Medical School, Boston, Massachusetts, United States
  • Kevin Mendez
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Medicine, Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States
  • Ines Lains
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Archana Nigalye
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Raviv Katz
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Shrinivas Pundlik
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Ivana K Kim
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Liming Liang
    Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, United States
  • Demetrios G. Vavvas
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • John Miller
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Joan W Miller
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Jessica A Lasky Su
    Department of Medicine, Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States
  • Deeba Husain
    Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Janice Kim, None; Kevin Mendez, None; Ines Lains, None; Archana Nigalye, None; Raviv Katz, None; Shrinivas Pundlik, Mass Eye & Ear, I - EyeNexo, LLC (P); Ivana Kim, Allergan (F), Biophytis (C), Castle Biosciences (C), Kodiak Sciences (C), Novartis (C); Liming Liang, None; Demetrios Vavvas, None; John Miller, Alcon (C), Allergan (C), Carl Zeiss Meditec, Inc. (C), Genentech (C), Heidelberg Engineering, Inc. (C); Joan Miller, Drusolv Therapeutics (S), Genentech/Roche (C), Genentech/Roche (R), Heidelberg Engineering (C), Heidelberg Engineering (R), KalVista Pharmaceuticals (C), KalVista Pharmaceuticals (R), Lowy Medical Research Institute (F), ONL Therapeutics (C), ONL Therapeutics (P), ONL Therapeutics (R), Sunovion (C), Sunovion (R), Valeant Pharmaceuticals/Mass. Eye and Ear (P), Valeant Pharmaceuticals/Mass. Eye and Ear (R); Jessica Lasky Su, None; Deeba Husain, Genentech (C), Genentech (R), Heidelberg (C)
  • Footnotes
    Support  Miller Retina Research Fund, Champalimaud Vision Award, National Institutes of Health (NIH) R01EY030088-01A1, the unrestricted departmental Grant from Research to Prevent Blindness, Inc. New York, and the Commonwealth Unrestricted Grant for Eye Research, R01HL123915 and R01HL141826.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 343. doi:
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      Janice Kim, Kevin Mendez, Ines Lains, Archana Nigalye, Raviv Katz, Shrinivas Pundlik, Ivana K Kim, Liming Liang, Demetrios G. Vavvas, John Miller, Joan W Miller, Jessica A Lasky Su, Deeba Husain; Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2021;62(8):343.

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

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Abstract

Purpose : Dark adaptation (DA), a functional outcome measure, is impaired early in age-related macular degeneration (AMD) prior to visual acuity loss. Metabolomics, the qualitative and quantitative analysis of metabolites, have provided insight on multifactorial diseases including AMD. In order to better understand AMD pathogenesis, we performed a study to analyze the association between plasma metabolite levels and DA in AMD.

Methods : Cross-sectional study including both eyes of 71 subjects, 53 with AMD (13 early AMD, 31 intermediate AMD, 9 late AMD) and 18 controls. Participants were imaged with color fundus photographs for AMD classification (Age-Related Eye Disease Study classification). Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Harrisburg, PA) DA 20 minutes protocol. Rod-intercept time (RIT) was assessed and area under the dark adaptation curve (AUDAC) were calculated. Associations between RIT and metabolite levels were tested using multilevel multivariate mixed-effects linear modelling. An alternative analysis was performed using AUDAC as the outcome.

Results : Prolonged RIT was significantly associated (P < 0.01) with lower levels of fatty acid-related lipids and higher levels amino acids related to glutamate, leucine, isoleucine, and valine metabolism. Specifically, 8 plasma metabolites were associated with RIT, including 2 amino acids (N-acetylglutamine [P= 0.005], +r and N-acetylleucine [P= 0.008], +r), 1 carbohydrate (mannitol/sorbitol [P= 0.003], +r), and 5 fatty acid-related lipids ([P < 0.008], -r). Similar results were found for 14 significant plasma metabolites when AUDAC was used as the outcome, with the addition of 2 nucleotides (beta-alanine [P= 0.002], +r, and xanthine [P= 0.008], -r).

Conclusions : To our knowledge, this is the first report to study the association of metabolites with DA. Our results suggest that reduced levels of fatty acid-related lipids and elevated levels of amino acids may be associated with worse DA (prolonged RIT or increased AUDAC), suggesting that oxidative stress and mitochondrial dysfunction may play a role in AMD and its visual impairment.

This is a 2021 ARVO Annual Meeting abstract.

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