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Abstract #45447 Published in IGR 13-2
Connective Tissue Growth Factor is increased in Pseudoexfoliation Glaucoma
Browne JG; Ho SL; Kane R; Oliver N; Clark AF; O'brien CJ; Crean JKInvestigative Ophthalmology and Visual Science 2011;
Purpose: Pseudoexfoliation syndrome (PXF) is a generalised disorder of the extracellular matrix (ECM) involving the trabecular meshwork (TM), associated with raised intraocular pressure, glaucoma and cataract. The aims of this study were to quantify aqueous humor Connective Tissue Growth factor (CTGF) in PXF glaucoma, to determine the effect of CTGF on ECM production in TM cells and identify intracellular CTGF signaling pathways Methods: Aqueous humor samples were obtained from patients undergoing routine cataract surgery or trabeculectomy. CTGF levels were quantified using ELISA. The effect of CTGF on fibrillin-1 expression in TM cells was investigated by real-time PCR. Western immunoblotting was used to investigate CTGF signaling. c-Jun/AP-1 activation was measured in CHO cells by ELISA following stimulation with CTGF. Results: PXF with glaucoma (n=18) had the highest aqueous humor CTGF of 5.15 ± 0.79 (SEM) ng/ml (p<0.01) compared with PXF without glaucoma (n=15) (2.76 ± 0.64 ng/ml), primary open angle glaucoma (POAG) (n=20) (3.05 ± 0.40 ng/ml) and controls (n=21) (2.60 ± 0.29 ng/ml). In vitro exposure of TM cells to CTGF resulted in a 50% upregulation of fibrillin-1, which was partially blocked with the MEK (Mitogen-activated protein Extracellular Kinase) inhibitor PD098059. Western blot analysis demonstrated increased phosphorylation of p42/44 MAPK, p38 MAPK and the JNK pathways in response to CTGF. c-Jun/AP-1 activity was significantly increased in response to CTGF treatment. Conclusions: Increased levels of CTGF in the aqueous humor of PXF patients likely has pathological significance through increased production of fibrillin-1 by TM cells through activation of p42/44 MAPK, p38 MAPK, and JNK pathways.
Classification:
9.4.4.1 Exfoliation syndrome (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.4 Glaucomas associated with disorders of the lens)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
