Metabolomic Analysis Of Aqueous Humor In Eyes With And Without Pseudoexfoliation Syndrome Using Liquid Chromatography-Mass Spectrometry (Lc-Ms)

Pseudoexfoliation syndrome (PES) is characterized by abnormal fibrillar material deposition within ocular tissues. This study aims to compare the metabolomic profiles of aqueous humor (AH) obtained during cataract surgery from patients with and without PES, to explore potential metabolic differences.

This study was conducted at Bezmialem Vakif University, Department of Ophthalmology and Department of Biochemistry, Istanbul, Turkey.

Sixty-five patients (34 with PES and 31 without PES) aged between 40 and 85 years undergoing cataract surgery were included. Patients with significant ocular or systemic diseases were excluded. AH samples were centrifuged and chemically processed. Metabolites were analyzed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Bioinformatics analyses and pathway identification utilized databases (KEGG, HMDB, MassBank, MoNA) and software tools (ProteoWizard, TidyMass, MetaboAnalyst). Statistical analyses were performed using R software.

Forty-one metabolites were identified and quantified. Notably, citric acid was significantly elevated (VIP=2.3), and leucine significantly reduced (VIP=2.2) in the PES group compared to controls. Pathway analysis highlighted the defective OPLAH pathway and citric acid cycle in PES pathogenesis. Alterations in leucine metabolism suggested contributions to oxidative stress, mitochondrial dysfunction, and inflammation associated with PES.

Increased citric acid and decreased leucine concentrations in AH samples from PES patients indicate the involvement of oxidative stress and altered metabolic pathways, especially the OPLAH pathway, in PES pathogenesis. Metabolomics offers a valuable approach to understanding the complex molecular mechanisms underlying ocular diseases.