Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13

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.

Identification and Interaction Analysis of Significant Genes and MicroRNAs in Pterygium

“…Pterygium is a fibrovascular proliferative condition of the ocular surface, leading to ocular irritation, astigmatism, and even visual disturbance when it affects the visual axis [3–5, 39]. Because of the complicated pathological mechanism, pterygium bothers both of the patient and the surgeon because of its unsightly appearance and its tendency to recur [40].…”

“…Pterygium is a common ocular surface disease, which is characterized by proliferation, inflammatory infiltrates, fibrosis, angiogenesis, and ECM breakdown in conjunctiva and progressively invaded the cornea [1, 2]. It is the result of an abnormal limbus basal epithelial stem cell that moves onto Bowman's layer and brings about the dissolution of this layer [3–5], affecting up to 200 million people globally and the prevalence in China has reached 108.65 million [6, 7]. Pterygium can impair vision, limit eye movements, and cause eye irritation, foreign body sensation, and dryness [8, 9].…”

The Association of MMP-8 Genotypes with Pterygium

“…Also, in early-stage pterygium tissues and cultured fibroblasts, MMP-2 or MMP-9 was at low or undetectable levels, while in advanced-stage pterygium (pterygium head passed the papillary region), MMP-2 and MMP-9 could be obviously detected in pterygium tissues and fibroblasts (16). In addition, down-regulation of the expression levels of MMP-3 and MMP-13 was capable of suppression of the proliferation and migration of pterygium fibroblasts (24,25). These findings support the idea that MMPs may play an important role in the progression of pterygium, and the genomic markers on MMPs can serve as valuable predictive biomarkers for the development or reoccurrence of pterygium.…”

Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD)

“…In addition, MMPs play a central role in the direct activation of signaling molecules, such as tumor necrosis factor (TNF) and other cytokines; MMPs therefore contribute to various aspects of immunity [ 48 ]. A detailed classification of MMPs and TIMPs, based on their substrates, general biological effect, localization in the eye, and processes in which they take part, is provided in the Supplementary Table S1 [ 16 , 17 , 32 , 38 , 41 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”