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J. Chua, T. T. Wong, L.-F. Seet; Valproic Acid Maintains Bleb Function Following Experimental Glaucoma Filtration Surgery in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3198.
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Valproic acid (VPA) belongs to a family of compounds known as histone deacetylase (HDAC) inhibitors shown to suppress fibrogenesis. Fibrosis is a leading cause of surgical failure in trabeculectomy. The aim of this study is to investigate the effect of VPA on the expression of fibrotic markers in vitro and its ability to maintain bleb function after trabeculectomy in a rabbit model in vivo.
Human tenons fibroblasts were assayed for collagen and fibronectin expressions when treated with VPA by quantitative real-time PCR. Modified trabeculectomy surgery was performed on New Zealand white rabbits. The animals were then immediately injected subconjunctivally with 100 µl of either 20% pluronic acid containing 120 µg/ml valproic acid or 20% pluronic acid in phosphate buffered saline as control. Thereafter, the animals were injected with the respective agents once a week. The operated eyes were monitored for intraocular pressure as well as bleb survival and bleb vascularity by slit lamp and anterior segment optical coherence tomography (AS-OCT) examinations. The eyes were subjected to histological analysis at 28 days.
Treatment with VPA reduced the expressions of collagen I and fibronectin in human Tenons fibroblasts. The optimal concentration in reducing collagen I expression was 120 µg/ml VPA. The IOP of VPA-treated rabbits was maintained at a consistently 50% lower pressure compared to the pre-operation IOP for up to 21 days. This was confirmed by the continued presence of the bleb as assessed by slit lamp and AS-OCT analyses. There was also reduced conjunctival vascularity in the VPA-treated rabbits compared to controls.
VPA is effective in maintaining bleb function and reducing bleb vascularity after trabeculectomy in a rabbit model. This is likely to be due to the anti-fibrotic property of VPA since it can reduce the expression of fibrotic markers in vitro. Our data is supportive for the use of VPA as an effective anti-fibrotic alternative in trabeculectomy.
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