A novel ocular function for decorin in the aqueous humor outflow

Area of Science:

• Ophthalmology
• Molecular Biology
• Pathogenesis of Glaucoma

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of blindness due to optic nerve axon degeneration.
• Elevated intraocular pressure (IOP), driven by increased aqueous humor outflow resistance, is a major risk factor for POAG.
• The molecular mechanisms underlying outflow resistance in POAG remain incompletely understood, with transforming growth factor (TGF)-β2 implicated.

Purpose of the Study:

• To investigate the role of decorin, a TGF-β antagonist, in the aqueous humor outflow pathway.
• To elucidate the impact of decorin deficiency on intraocular pressure and glaucoma-related pathology.
• To examine the effect of decorin on TGF-β signaling and gene expression in trabecular meshwork cells.

Main Methods:

• Utilized decorin-deficient (Dcn-/-) mice to assess in vivo effects.
• Analyzed intraocular pressure, optic nerve axon integrity, and glial lamina morphology in Dcn-/- mice.
• Investigated the interaction between decorin and TGF-β signaling in human trabecular meshwork cells.
• Quantified decorin and TGF-β expression in human POAG patients.

Main Results:

• Decorin deficiency in mice led to increased intraocular pressure, optic nerve axon loss, and glial lamina changes characteristic of glaucoma.
• Soluble decorin inhibited TGF-β2-induced expression of downstream genes (CCN2/CTGF, FN, COL IV) in human trabecular meshwork cells.
• A negative reciprocal regulation between decorin and TGF-β was observed, with decorin significantly downregulated in POAG patients.

Conclusions:

• Decorin plays a critical role in regulating aqueous humor outflow and preventing glaucoma pathogenesis.
• Decorin deficiency exacerbates glaucoma features by modulating TGF-β signaling and increasing intraocular pressure.
• Decorin represents a potential therapeutic target for primary open-angle glaucoma.