Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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).
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.
This PDF is available to Subscribers Only