Abstract
We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA. A scratch wound healing migration assay was performed to determine the effects of bevacizumab and/or CsA. Protein expression of both MMPs in pterygium tissues and in cells migrating from organ-cultured pterygium tissues was greater than that observed in normal cells. Inhibition of the activities of both MMPs decreased their expression levels; these were also significantly reduced in bevacizumab-injected pterygium tissues. Bevacizumab significantly reduced the expression of both MMPs and cell migration. Pretreatment with CsA prior to bevacizumab exposure markedly inhibited cell migration and the expression of both MMPs. CsA enhanced the inhibitory effects of bevacizumab on pterygium fibroblast migration in vitro, possibly by inhibiting expression of both MMPs. These findings suggest that combined CsA and bevacizumab treatment may provide a potential therapeutic strategy for reducing the rate of pterygium recurrence.
Highlights
Pterygium is a common ocular surface disease in humans that is attributed to chronic ultraviolet-B exposure and can cause vision loss
Many matrix metalloproteinase (MMP) were expressed in pterygium tissues, our study mainly focused the activities of MMP-3 and MMP-13 which may play an important role in the process of pterygium progression
The stained areas were 41.37-54.77% (MMP-3) and 54.81-71.90% (MMP-13) larger in the pterygium tissue than in the normal conjunctival tissue (Fig 1C). Expression of both MMP-3 and MMP-13 proteins was detected in the epithelium and stroma of the pterygium tissue, but these were weakly expressed in normal conjunctival tissue (Fig 1A)
Summary
Pterygium is a common ocular surface disease in humans that is attributed to chronic ultraviolet-B exposure and can cause vision loss. It results from the migration of abnormal limbal basal epithelial stem cells (pterygium cells) into Bowman’s layer (BL) and causes the dissolution of this layer. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are able to degrade all components of the ECM in connective tissues [12, 13]. They are important in various physiological and pathological processes, including tissue remodeling, wound healing, angiogenesis, cell invasion, and differentiation [14]. Given that many studies have shown a strong association between MMPs and tumor progression/invasion [18], the invasive nature of the pterygial lesion is likely to involve altered MMP activity
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