Aberrant glycosylation in the human trabecular meshwork.

Area of Science:

• Ophthalmology
• Glycobiology
• Cell Biology

Background:

• Trabecular meshwork (TM) dysfunction is implicated in glaucoma pathogenesis.
• Altered protein glycosylation is a potential contributor to TM cellular changes in glaucoma.

Purpose of the Study:

• To investigate differences in protein glycosylation and glycosylation enzyme levels in glaucomatous versus control trabecular meshwork (TM).
• To assess the functional impact of altered glycosylation on TM cells.

Main Methods:

• Comparative analysis of glaucomatous and normal donor TM tissues using lectin fluorescence, fluorophore-assisted carbohydrate analyses, and quantitative mass spectrometry (MS).
• In vitro studies using primary TM cells and glycosylation inhibitors to evaluate effects on cell morphology and motility.

Main Results:

• Glaucomatous TM exhibited simultaneous hyper- and hypo-glycosylation, contrasting with elevated overall glycoprotein levels observed via lectin fluorescence.
• Specific enzyme alterations included increased beta-glycosidase 1 and decreased galactosyltransferase family 6 domain containing protein 1 in glaucomatous TM.
• Hypo-glycosylation induced by inhibitors in primary TM cells altered cell shape, motility, and barrier function.

Conclusions:

• Global protein glycosylation is aberrant in the glaucomatous TM compared to controls.
• These glycosylation changes, affecting both cellular and extracellular matrix proteins, likely contribute to glaucoma pathology by altering TM cell properties.