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Dong-Hui Lim, Tae Eun Kim, Changwon Kee; Evaluation of Down-regulation of Connective Tissue Growth Factor on the Postoperative Wound Healing after Experimental Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2011;52(14):623.
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Connective tissue growth factor(CTGF), a downstream effector of transforming growth factor-β, is a mitogenic peptide that has been involved in various fibrotic disorders. This study was aimed to determine whether down-regulation of CTGF expression could modulate postoperative scarring in a rabbit received modified glaucoma filtration surgery.
A replication-deficient recombinant adenovirus was constructed that transcribed a hairpin small interfering RNA (siRNA) specific to CTGF gene under the control of modified CMV promoter. Primary tenon cell cultures originated from New Zealand White rabbit were transduced with 10 - 100 plaque-forming units (pfu) per cell of the viral vector and, 72 hours later, CTGF expression was analyzed by Western blot analysis. Rabbits underwent modified glaucoma filtration surgery and received postoperative subconjunctival injection of 5 ul viral suspension (2X1011 pfu/ml) 5 days before immunohistochemical and histological examination of surgical outcome.
Western blot analysis showed that CTGF was dramatically depleted to less than 10% of its original level in cells transduced with an adenovirus expressing CTGF-specific siRNA, demonstrating RNA interference (RNAi)-mediated CTGF inactivation in vitro. Immunohistochemical analysis also showed that CTGF was significantly depleted in eyes transduced with an adenovirus expressing CTGF siRNA, further demonstrating RNAi-mediated CTGF inactivation in vivo. Histological evaluation showed that less scar tissue was observed at the sclerotomy site and conjunctiva in the transduced eyes, demonstrating that inhibition of CTGF modulates wound healing process after surgery.
Down-regulation of CTGF is sufficient to inhibit postoperative scarring in vivo, suggesting that RNAi with CTGF may potentially pave the road for a novel therapeutic strategy to improve glaucoma surgery results.
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