Abstract
Purpose:
To investigate the effects of Bevacizumab or/and Cyclosporin A (Cys A) on the matrix metalloproteinase (MMP) 3 and MMP-13 expression in cultured human pterygial fibroblast cells and tissues.
Methods:
Pterygial and normal conjunctival tissue of Korean patients (10 males and 10 females) were analyzed. Immunostaining, Western blotting and RT-PCR were performed to detect the localization and expression level of MMPs. After being scratched, human pterygial fibroblast cells were exposed to Cys A concentrations of 1 µg/ml (0.0001%) and 100 µg/ml (0.01%) for 3 or 10 minutes and/or bevacizumab 1 µg/ml with serum depletion DMEM-F-12 (1:1) media for 48 hours. Changes in expression of MMP-3 and MMP-13 of fibroblast after the stimulation were studied.
Results:
MMP-3 and MMP-13 expression in pterygium tissues was greater than those of normal conjunctiva and was closely associated to the progression of pterygium. Bevacizumab-injected pterygium tissues were significantly reduced MMP-3 and MMP-13 expression. In vitro, bevacizumab and/or Cys A-treated pterygial fibroblast was also markedly inhibited cell migration and MMPs expression. Interestingly, pre-exposed pterygial fibroblast with Cys A and followed by bevacizumab treatment blocked the cell migration and MMP-3 and MMP-13 expression (P<0.01), significantly higher.
Conclusions:
Other previously reported studies demonstrated that subconjunctival bevacizumab injection was useful in management of patients with primary and recurrent pterygium without significant local or systemic adverse effects, however, the exact mechanism still remains unclear. Our results suggested high expression of MMPs induced proliferation and migration of pterygial fibroblast. Secondly, expressionof MMPs were down-regulated by bevacizumab or Cys A treatment. Here, we show that combined treatment of Cys A and bevacizumab was more effective in inhibition of MMPs. These finding also provide therapeutic potential for pterygium progression.
Keywords: 474 conjunctiva •
665 pterygium •
489 cyclosporine