Arsenic Trioxide Inhibits Proliferation of Rabbit Tenon's Capsule Fibroblasts After Trabeculectomy by Downregulating Expression of Extracellular Matrix Proteins.

PURPOSE

The purpose of this study was to study the effectiveness of arsenic trioxide (ATO) in regulation of trabeculectomy in an animal model.

METHODS

This study was designed as random, comparative, and prospective study. Primary Tenon's capsule fibroblasts (TFs) were cultured and their viability after arsenic trioxide (ATO) treatment was detected using 3-(4, 5-dimethylthiazolyl-2-)-2, 5-diphenyltetrazoliumbromide (MTT) and bromodeoxyuridine incorporation (BrdU) assays. The dose of ATO was determined by 50% growth inhibition (IC50 values) and cell-cycle analysis. The expression of extracellular matrix (ECM) components and proliferating cell nuclear antigen (PCNA) was determined by Western blotting analysis. The status of filtration bleb was detected by hematoxylin and eosins (HE) stain.

RESULTS

Based on the MTT and BrdU assays, IC50 values was observed in rabbit TFs (rTFs) cells after treatment with ATO at a concentration of 6 μM arsenic trioxide for 72 hours. In addition, the ATO treatment caused not only a significant reduction in the expression of ECM proteins, fibronectin, collagen IV, and laminin in rTFs, but also reduced the expression of PCNA expression in a time dependent manner. The histologic observation showed high-level proliferation of rTFs in both vehicle and control groups, and proliferative ability of rTFs of experimental group was less than in vehicle and control group. Moreover, no inflammation was observed in the experimental group, and the filtering bleb was detected in the experimental group after 14 days of trabeculectomy.

CONCLUSIONS

Arsenic trioxide inhibited the proliferation of rTFs after trabeculectomy and may improve the success ratio of trabeculectomy in an animal model.