Differential protein expression and metabolite profiling in glaucoma: Insights from a multi-omics analysis

Area of Science:

• Ophthalmology
• Biochemistry
• Proteomics
• Metabolomics

Background:

• Aqueous humor (AH) composition influences intraocular pressure (IOP), a key factor in glaucoma.
• Understanding AH substance changes and their interactions is crucial for glaucoma research.

Purpose of the Study:

• To investigate individual changes and network interactions of AH substances in glaucoma using a multi-omics approach.
• To identify potential biomarkers for glaucoma management by analyzing AH proteome and metabolome.

Main Methods:

• LC/MS analysis of AH samples from patients with exfoliation syndrome (XFS), exfoliation glaucoma (XFG), primary open-angle glaucoma (POAG), and controls (cataracts).
• Integrated proteomics and metabolomics (data-independent and data-dependent acquisition) to examine differentially expressed components and network interactions.
• Analysis of biological functions associated with altered proteins and metabolites.

Main Results:

• Proteomics revealed upregulated proteins in XFG and POAG related to lipid metabolism, complement activation, and extracellular matrix regulation.
• Metabolomics identified significant changes in antioxidant-related amino acids in glaucoma groups.
• Key molecules like VTN, APOA1, C6, and L-phenylalanine showed significant alterations; integrated analysis highlighted networks involving inflammation and lipid metabolism.

Conclusions:

• Altered substances in AH, particularly those in inflammation and lipid metabolism pathways, interact within complex networks in glaucoma.
• These findings provide insights into IOP regulation mechanisms and potential novel biomarkers for glaucoma detection and management.