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W.D. Esson, S.A. Iyer, T.D. Blalock, G.S. Schultz, M.B. Sherwood; Addition of Exogenous Connective Tissue Growth Factor (CTGF) Accelerates the Failure of Surgical Glaucoma Filtering "Blebs" in Rabbits . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1197.
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Purpose: Failure of glaucoma filtering surgery is generally caused by excessive conjunctival scarring and contraction of the bleb site. Previous studies have demonstrated that connective tissue growth factor (CTGF) plays a key role in mediating many of the actions of transforming growth factor beta (TGF-b) on scar formation. The purpose of this study was to assess whether exogenous CTGF accelerates clinical "bleb" failure following glaucoma filtering surgery. Methods: Glaucoma filtering surgery was performed in one eye of four adult New Zealand White rabbits by creating a limbal-based conjunctival flap and inserting a 22G, 25 mm IV cannula through a scleral tunnel into the anterior chamber to create a filtering bleb. The filtering site was treated with a 5-minute intra-operative application of 0.4mg/ml Mitomycin-C to increase bleb survival time. Eight days following surgery, two randomly selected blebs were injected with 0.2 ml of balanced salt solution (BSS) containing 5µg of recombinant, human CTGF and the other two blebs were injected with 0.2 ml of BSS. Bleb survival was assessed for 21 days post surgery by measuring intra ocular pressure, bleb width and depth and estimating bleb height. Results: Blebs treated with BSS contracted to 50% of their original area by an average of 13 days after injection. In contrast, blebs treated with CTGF failed more rapidly, reaching 50% of their original size by an average of 6 days after injection. CTGF treated blebs were more vascular in appearance for the first 2-3 days following injection and failed completely by an average of 16 days after injection but the BSS treated blebs continued to survive at 21 days. Conclusions: Addition of exogenous CTGF significantly accelerates the rate of bleb failure in a rabbit model of glaucoma filtering surgery, suggesting that CTGF is a major regulator of conjunctival scarring in glaucoma filtering surgery. Inhibition of CTGF synthesis or its action may help prevent bleb failure.
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