In Vitro Study of Combined Application of Bevacizumab and 5-Fluorouracil or Bevacizumab and Mitomycin C to Inhibit Scar Formation in Glaucoma Filtration Surgery.

Yuanyuan Zhang,Xun Xu,Lei Zuo,Shaopin Zhu

doi:10.1155/2019/7419571

Abstract

This is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). The cytotoxicity of drug combinations in human Tenon's fibroblasts (HTFs) and human umbilical vein endothelial cells (HUVECs) was evaluated. Their effects on the levels of vascular endothelial growth factor (VEGF) in HUVECs, cell proliferation and migration in HTFs, and the expression of collagen type I alpha 1 (Col1A1) gene in HTFs were evaluated. In addition, the effects of combined drugs on VEGF(R) mRNA in HTFs were detected to explore the possible underlying drug mechanisms. The results showed that BVZ combined with 5-Fu demonstrated more significant antiscarring effects than BVZ or 5-Fu alone. However, the inhibitory effects of BVZ combined with MMC were similar to those of MMC alone. The cytotoxicity of the drug combinations was significantly greater than that of single drug, suggesting that combined application of BVZ and antimetabolites after GFS was safer when applied at different sites (such as subconjunctival injection at bilateral sides of the filtering bleb) or at varied time points.

Highlights

Academic Editor: Sentaro Kusuhara is is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). e cytotoxicity of drug combinations in human Tenon’s fibroblasts (HTFs) and human umbilical vein endothelial cells (HUVECs) was evaluated. eir effects on the levels of vascular endothelial growth factor (VEGF) in HUVECs, cell proliferation and migration in HTFs, and the expression of collagen type I alpha 1 (Col1A1) gene in HTFs were evaluated
The inhibitory effects of BVZ combined with MMC were similar to those of MMC alone. e cytotoxicity of the drug combinations was significantly greater than that of single drug, suggesting that combined application of BVZ and antimetabolites after GFS was safer when applied at different sites or at varied time points
Immunofluorescence assay was performed to identify HTF cells. e result of staining of anti-vimentin antibody was positive, anti-keratin antibody was negative, and morphological observation of these cells confirmed them as fibroblasts [28]

Summary

Introduction

Academic Editor: Sentaro Kusuhara is is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). e cytotoxicity of drug combinations in human Tenon’s fibroblasts (HTFs) and human umbilical vein endothelial cells (HUVECs) was evaluated. eir effects on the levels of vascular endothelial growth factor (VEGF) in HUVECs, cell proliferation and migration in HTFs, and the expression of collagen type I alpha 1 (Col1A1) gene in HTFs were evaluated. Academic Editor: Sentaro Kusuhara is is an in vitro study conducted to observe the safety and antiscarring effects of combined application of bevacizumab (BVZ) and 5-fluorouracil (5-Fu) or BVZ and mitomycin C (MMC) during glaucoma filtration surgery (GFS). Subconjunctival injection of BVZ reaches an effective level in the intraocular tissues of the treated eyes [14] Based on these studies, subconjunctival injection of a certain dose of BVZ for inhibiting scar formation during trabeculectomy has been used [4, 15, 16]. Erefore, clinicians have combined the application of BVZ and MMC or BVZ and 5-Fu to improve the clinical outcomes of GFS for refractory glaucoma [20, 21], trying to reduce the risk of antimetabolite use and effectively inhibit scar formation after GFS. Spitzer et al [22] have reported on the toxicity of BVZ on human ocular cells; the safety of BVZ combined with 5-Fu (BVZ + 5-Fu) and BVZ combined with MMC (BVZ + MMC) in human ocular cells still remains unclear

Objectives

Methods

Results