Korean J Physiol Pharmacol.  2015 Jul;19(4):357-363. 10.4196/kjpp.2015.19.4.357.

Effect of Bevacizumab on Human Tenon's Fibroblasts Cultured from Primary and Recurrent Pterygium

Affiliations
  • 1Department of Ophthalmology, Pusan National University School of Medicine & Medical Research Institute, Yangsan Pusan National University Hospital, Yangsan 626-770, Korea.
  • 2Department of Pharmacology, Pusan National University College of Medicine, and MRC for Ischemic Tissue Regeneration, Yangsan 626-870, Korea.
  • 3Department of Ophthalmology, School of Medicine, Pusan National University & Medical Research Institute, Pusan National University Hospital, Pusan 602-739, Korea. jongsooluw@gmail.com

Abstract

The purpose
of this study was to compare the inhibitory effect of bevacizumab on human Tenon's fibroblasts (HTFs) cultured from primary and recurrent pterygium. Cultured HTFs were exposed to 2.0, 5.0, 7.5, and 15.0 mg/mL concentration of bevacizumab for 24 hours. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assays were then performed to assess fibroblast metabolism and viability. The matrix metalloproteinase (MMP), procollagen type I C terminal propeptide (PIP), and laminin immunoassays were performed to examine extracellular matrix production. Changes in cellular morphology were examined by phase-contrast and transmission electron microscopy. Both metabolic activity and viability of primary and recurrent pterygium HTFs were inhibited by bevacizumab in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. Both types of HTFs had significant decreases in MMP-1, PIP, and laminin levels. Distinctly, the inhibitory effect of bevacizumab on MMP-1 level related with collagenase in primary pterygium HTFs was significantly higher than that of recurrent pterygium. Significant changes in cellular density and morphology both occurred at bevacizumab concentrations greater than 7.5 mg/mL. Only primary pterygium HTFs had a reduction in cellular density at a bevacizumab concentration of 5.0 mg/mL. Bevacizumab inhibits primary and recurrent pterygium HTFs in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. As the primary HTFs produces larger amounts of MMP-1 compared to recurrent HTFs, significant reduction in MMP-1 level in primary pterygium HTFs after exposure to bevacizumab is likely to be related to the faster cellular density changes in primary pterygium HTFs.

Keyword

Anti-fibrotic effect; Bevacizumab; Extracellular matrix; Human Tenon's fibroblasts; Pterygium
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