Effect of TIMP-1 and MMP in Pterygium Invasion

Abstract

PURPOSE. The migration and invasion of tumor cells correlate with the interaction between MMP and TIMP. Therefore, the purpose of this study was to determine the role of MMP-9, MMP-10, and TIMPs in pterygium formation and progression. METHODS. MMP-9, MMP-10, and TIMP proteins were studied using immunohistochemistry on 82 pterygial specimens and 30 normal conjunctivas. Pterygium epithelial cells (PECs), cultured in a serum-free culture medium, and siRNA were used to knock down TIMP gene expression to understand the role of TIMP in pterygium invasion. RESULTS. Among the 82 pterygial samples, 29 specimens (35.4%) were positive for MMP-9 expression, 28 were positive for MMP-10 (34.1%), and 59 were positive for TIMP1 (72.0%). Staining for MMPs was limited to the cytoplasm of the epithelial layer. The TIMP staining was detected in the pterygium epithelium, fibroblasts and corneal epithelium. In the cell model, cell invasion and migration ability increased in TIMP knockdown PECs compared with the parental control. CONCLUSIONS. MMP-9 and MMP-10 may each play a role in pterygium formation, and TIMPs may contribute to pterygium invasion inhibition.

Molecular Basis of Pterygium Development

“…12 MMPs inhibitors (TIMPs) have been found with high expression in pterygium samples; along with the high levels of MMPs, these proteins may be active participants in the extensive matrix turnover and infiltration that characterize pterygium. 4 The expression levels of these proteinases and their inhibitors could mediate the velocity of pterygium formation and expansion.…”

“…It is characterized by an altered basal epithelial cell proliferation, vascularization, and invasion of the adjacent corneal epithelium. [1][2][3][4][5] The progression of this disease first involves the presence of gray circumscribed dots in the cornea near the limbus, with simultaneous tense conjunctiva that appear opposite to the area of corneal affection, and there is also displacement of the plica. Later, a wing-shaped extension of the fleshy growth of the bulbar conjunctiva onto the cornea takes place.…”

“…6,7 The pathogenesis of this disease remains unclear, although it is generally considered to be caused by ultraviolet (UV) radiation, as supported by studies that have found a direct relationship between one's proximity to the equator and a higher prevalence of pterygium. [8][9][10] Alternatively, a wide array of pathogenic factors has been proposed, including viral infections, 11 epigenetic aberrations, 12-14 epithelialmesenchymal transition, 15,16 immunologic [17][18][19][20] and anti-apoptotic mechanisms, 21-24 angiogenic 2,25,26 and lymphangiogenic stimulation, 27,28 deregulation of extracellular matrix modulators 4,29 and growth factors, 30 inflammation cascades, 31-33 recruitment of bone-marrow-derived stem and progenitor cells, [34][35][36] and modifications in cholesterol metabolism. [37][38][39] However, most of these factors are more related to the development and maintenance of the disease than to its origin.…”

MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery

“…While Tsai et al [23] found practically little or no expression of these species, Yang et al [24] found both MMP-2 and MMP-9 activities in normal tissue. In these cases, pathology was related to higher expression and/or activity of the tested MMPs.…”

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.…”