Connective tissue growth factor is increased in pseudoexfoliation glaucoma

Area of Science:

• Ophthalmology
• Extracellular Matrix Biology
• Glaucoma Research

Background:

• Pseudoexfoliation (PXF) syndrome is a generalized extracellular matrix (ECM) disorder affecting the trabecular meshwork (TM).
• PXF syndrome is associated with elevated intraocular pressure, glaucoma, and cataract.
• Connective tissue growth factor (CTGF) plays a role in ECM regulation.

Purpose of the Study:

• Quantify aqueous humor CTGF levels in PXF glaucoma patients.
• Determine CTGF's effect on ECM production in TM cells.
• Identify intracellular CTGF signaling pathways involved in PXF.

Main Methods:

• Aqueous humor samples collected during cataract surgery or trabeculectomy.
• CTGF levels measured by ELISA; fibrillin-1 expression by real-time PCR.
• Intracellular signaling pathways (MAPK, JNK, c-Jun/AP-1) analyzed via Western blot and ELISA.

Main Results:

• Aqueous humor CTGF levels were significantly higher in PXF with glaucoma (5.15 ng/mL) compared to controls (2.60 ng/mL).
• CTGF exposure upregulated fibrillin-1 expression in TM cells by 50%, partially inhibited by MEK inhibitor.
• CTGF activated p42/44 MAPK, p38 MAPK, JNK pathways, and increased c-Jun/AP-1 activity.

Conclusions:

• Elevated aqueous humor CTGF in PXF patients likely contributes to pathology.
• CTGF promotes fibrillin-1 production in TM cells.
• Activation of MAPK and JNK pathways mediates CTGF's effects in PXF.