Comprehensive Serum Proteomics Uncovers Epigenetic and Inflammatory Pathways Underlying Primary Open-Angle Glaucoma

Area of Science:

• Ophthalmology
• Neuroscience
• Proteomics

Background:

• Primary open angle glaucoma (POAG) causes irreversible blindness due to retinal ganglion cell loss.
• Current treatments for POAG are insufficient, and molecular data from diverse populations are limited.
• Understanding POAG's molecular basis is crucial for developing effective, population-specific therapies.

Purpose of the Study:

• To conduct a comprehensive serum proteomic analysis in Indian POAG patients.
• To identify molecular markers and pathways associated with glaucomatous neurodegeneration.
• To explore potential biomarkers for early diagnosis and therapeutic targets.

Main Methods:

• Serum proteomic analysis using label-free nano-LC-MS/MS profiling.
• Clinical validation including optical coherence tomography (OCT) for structural assessment.
• Machine-learning network analysis to identify disease-associated proteins and pathways.

Main Results:

• Identified 22 unique proteins differentially expressed in POAG patients.
• Revealed dysregulated pathways including neurodegeneration, inflammation, and epigenetic modifications (histone deacetylation, DNA methylation).
• Highlighted decreased levels of structural, neuronal, and immune proteins, with lumican and optineurin showing strong POAG association.

Conclusions:

• POAG is characterized by metabolic and epigenetic dysregulation, driving neurodegeneration.
• Lumican and optineurin show potential as serum biomarkers for POAG.
• Findings support biomarker-based strategies for early POAG detection and development of neuroprotective therapies.