Trichostatin A Ameliorates Conjunctival Fibrosis in a Rat Trabeculectomy Model.

PURPOSE: To investigate whether histone deacetylase (HDAC) activity is associated with postoperative scarring and to evaluate the effect of HDAC inhibition by topical trichostatin A (TSA) on conjunctival fibrosis after trabeculectomy in a rat model.

METHODS

Trabeculectomy was performed on the left eye of Sprague-Dawley rats. In the first experiment, adenoviruses HDAC 1, HDAC 2, and green fluorescent protein were added to the subconjunctival space during trabeculectomy. Expression of α-smooth muscle actin (α-SMA) was evaluated. In the second experiment, rats undergoing trabeculectomy were randomized into control, vehicle control, steroid, 500 nmol/L TSA, and 1 μmol/L TSA groups. On postoperative day 14, bleb vascularity, toxic effect of topical TSA on corneal epithelium, expression of α-SMA, transforming growth factor (TGF)-β1, and phosphorylated-Smad2/3 and the infiltration of CD45+ cells were determined. Masson's trichrome staining and immunofluorescence staining for α-SMA and CD45 were also performed.

RESULTS

Overexpression of HDAC1 contributed to accelerated conjunctival fibrosis after trabeculectomy. HDAC inhibition by topical administration of 1 μmol/L TSA significantly decreased bleb vascularity, leukocyte infiltration, and expression of α-SMA and TGF-β1 in the conjunctiva. Its effectiveness on conjunctival fibrosis was comparable to that of topical steroid. Masson's trichrome staining showed decreased collagen deposition in the bleb tissues of steroid and 1 μmol/L TSA treatment groups. Topical TSA did not have any toxic effect on the corneal epithelium.

CONCLUSIONS

HDAC activity is involved in postoperative conjunctival fibrosis. HDAC inhibition by topical administration of TSA eye drops is a safe and effective therapeutic modality to modulate wound healing after trabeculectomy.