Exogenous Metabolites Associated with Age-related Macular Degeneration (AMD)

Abstract

Purpose : Metabolomics can provide insights into the pathophysiology of multifactorial diseases. We and others have shown that patients with age related macular degeneration (AMD) have distinct metabolomic profiles. However, studies performed to date have primarily focused on endogenous metabolites. Given the known multifactorial nature of AMD, this work aimed to examine associations between exogenous plasma and urinary metabolomic profiles and AMD.

Methods : Cross-sectional study including patients with AMD and a control group from Boston, US and Coimbra, Portugal (PT). All participants were imaged with color fundus photographs that were used for AMD grading. The eye with the most advanced AMD stage was used for analysis. Fasting plasma and urine samples were collected and used for metabolomic profiling (Ultrahigh Performance Liquid Chromatography – Mass Spectrometry, Metabolon, Inc). Multivariate logistic (outcome AMD/no AMD) and ordinal logistic (outcome stages of disease) regression models were performed accounting confounding. Each cohort was analyzed separately and then results were combined via meta-analysis.

Results : We included 197 subjects from Boston, US (n=150 AMD) and 297 from Coimbra, PT (n= 244 AMD), and data on 115 plasma and 225 urinary exogenous metabolites. In the Boston cohort the most consistent associations were seen with vanilloylglycine, with both plasma and urine levels showing an association with AMD stages, and urine levels also with AMD diagnosis (p<0.006). In Coimbra, 6 plasma and 8 urine exogenous metabolites showed significant associations with AMD diagnosis and AMD stages accounting for multiple comparisons. In this cohort, pyrraline, an advanced glycation end product, showed the most consistent results, with both urine and plasma levels showing associations with AMD diagnosis and AMD stages (p< 0.002). Both vanilloylglycine and pyrraline have known correlations with oxidative stress. Pyrraline has also been linked to neurodegenerative diseases. After multiple comparisons, no significant associations were seen in the meta-analysis.

Conclusions : To our knowledge, we present the first analysis that focused on exogenous metabolite associations with AMD. This is important as it provides information on possible modifiable risk strategies. The lack of unifying results in our both cohorts is likely related to the distinct habits of US and PT populations.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.