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J. Sapitro, J. J. Dunmire, V. Sutariya, W. J. Geldenhuys, M. Hewit, B. Y. J. T. Yue, H. Nakamura; Suppression of Ocular Scarring After Glaucoma Filtration Surgery in Rabbits by Activin Receptor-Like Kinase 5 Inhibitor. Invest. Ophthalmol. Vis. Sci. 2010;51(13):604.
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Our laboratory has previously demonstrated that activin receptor-like kinase 5 (ALK-5) inhibitors are effective in suppressing expression of downstream, scarring-related proteins of transforming growth factor-β in cultured rabbit subconjunctival fibroblasts. The purpose of this study is to determine whether ALK-5 could suppress ocular scarring in vivo and thereby improve filtering bleb survival after glaucoma filtration surgery (GFS) in a rabbit model.
ALK-5 inhibitor SB-505124 was used. In an in vivo rabbit GFS model, SB-505124 was delivered in a lactose tablet during the surgery. Eyes were examined by slit-lamp and the intraocular pressure (IOP) was measured until the time of bleb failure or up to 28 days after surgery. Paraffin sections from tissues collected on post surgery day 5 were histologically evaluated by hematoxylin and eosin staining. In addition, dissected subconjunctival tissues were placed in a cell culture flask with media and cell outgrowth from the explants was examined.
Filtering blebs in the GFS with SB-505124 (GFS-SB505124) group were maintained for more than 10 days (13.3 ± 4.2 days, n = 3), and the period of bleb survival was significantly longer than that in GFS controls (4.0 ± 1.0 days, n = 3, log rank = 11.801, p<0.01). Longer IOP reduction was also observed in the GFS-SB505124 group. Histologically, subconjunctival cell infiltration and scarring at the surgical site in the GFS-SB505124 (n = 2) and mitomycin (MMC, n = 2) groups were much subsided compared to GFS controls (n = 2). The conjunctival epithelium appeared to be thinner in the MMC group compared to that in the GFS-SB505124 and GFS controls. Subconjunctival blood vessels were noted in the GFS-SB505124 and control groups, but seldom in the MMC group. Cell outgrowth from explants dissected from eyes to which SB-505124 was applied during GFS was robust while outgrowth was poor from those treated with MMC.
The ALK-5 inhibitor SB-505124 was efficacious in vivo in improving bleb survival with little toxicity. The inhibitor may provide a novel therapy for preventing ocular inflammation and scarring.
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