Aqueous humor protein dysregulation in primary angle-closure glaucoma

Area of Science:

• Ophthalmology
• Proteomics
• Molecular Biology

Background:

• Primary angle-closure glaucoma (PACG) is a leading cause of irreversible vision loss due to elevated intraocular pressure and optic nerve damage.
• The underlying molecular mechanisms of retinal ganglion neuropathy in PACG are not fully understood.
• Aqueous humor (AH) composition may reflect pathological changes in PACG.

Purpose of the Study:

• To conduct the first comprehensive proteomic analysis of aqueous humor (AH) from PACG patients.
• To identify pathogenic alterations in AH composition associated with PACG.
• To elucidate the molecular mechanisms of retinal ganglion neuropathy in PACG.

Main Methods:

• High-resolution, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for quantitative proteomic analysis.
• Aqueous humor samples were collected from PACG patients and a matched control group with cataracts.
• Proteomic data underwent pathway and cluster analyses to identify biological processes and dysregulated mediators.

Main Results:

• A total of 1363 distinct proteins were identified in the AH proteome.
• Over 50% of proteins (773) were differentially expressed in PACG patients compared to controls (501 up-regulated, 272 down-regulated).
• PACG-associated AH showed enrichment in atypical collagens/fibronectins, altered cellular transport, protease activity, and dysregulated oxygen homeostasis, implicating oxidative stress in nerve damage.

Conclusions:

• The altered AH proteome in PACG patients indicates significant oxidative stress contributing to neuronal damage preceding vision loss.
• Key mediators identified in AH offer potential prognostic biomarkers for PACG.
• These findings suggest novel therapeutic targets for mitigating PACG-associated vision loss.