Metabolomic Profiling of the Aqueous Humor in Patients with Wet Age-Related Macular Degeneration Using UHPLC–MS/MS

Assessing
metabolomic alterations in age-related macular degeneration
(AMD) can provide insights into its pathogenesis. We compared
the metabolomic profiles of the aqueous humor between wet AMD patients
(n = 26) and age- and sex-matched patients undergoing
cataract surgery without AMD as controls (n = 20).
A global untargeted metabolomics study was performed using ultra-high-performance
liquid chromatography tandem mass spectrometry. Univariate analysis
after the false discovery correction showed 18 significantly altered
metabolites among the 291 metabolites measured. These differential
metabolomic profiles pointed to three interconnected metabolic pathways:
a compromised carnitine-associated mitochondrial oxidation pathway
(carnitine, deoxycarnitine, N6-trimethyl-l-lysine), an altered
carbohydrate metabolism pathway (cis-aconitic acid,
itaconatic acid, and mesaconic acid), which plays a role in senescence
and immunity, and an activated osmoprotection pathway (glycine betaine,
creatine), which potentially contributes to the pathogenesis of the
disease. These results suggested that metabolic dysfunction in AMD
is mitochondrial-centered and may provide new insights into the pathophysiology
of wet AMD and novel therapeutic strategies.