Molecular mechanism of the inhibition effect of Celecoxib on corneal collagen degradation in three dimensions

Int J Ophthalmol. 2012;5(4):434-9. doi: 10.3980/j.issn.2222-3959.2012.04.06. Epub 2012 Aug 18.

Abstract

Aim: To clarify the molecular mechanism of Celecoxib on corneal collagen degradation and corneal ulcer.

Methods: Rabbit corneal fibroblasts were harvested and suspended in serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal fibroblast suspension were mixed on ice. The resultant mixture solidify in an incubator, after which test reagents and plasminogen was overlaid and the cultures were returned to the incubator. The supernatants from collagen gel incubations were collected and the amount of hydroxyproline in the hydrolysate was measured. Immunoblot analysis of MMP1, 3 and TIMP1, 2 was performed. MMP2, 9 was detected by the method of Gelatin zymography. Cytotoxicity Assay was measured.

Results: Celecoxib inhibited corneal collagen degradation in a dose and time manner; Celecoxib inhibited the IL-1ß induced increases in proMMP1, 2, 3, 9 and active MMP1, 2, 3, 9 in a concentration-depended manner. Celecoxib can also inhibit the IL-1ß induced increases in the TIMP1, 2.

Conclusion: Celecoxib can inhibit corneal collagen degradation induced by IL-1β, this effect is the consequence of the reduction of MMP1, 2, 3, 9 and TIMP1, 2. The results of the present study provide new insight into Celecoxib in corneal ulcer treatment.

Keywords: Celecoxib; IL-1β; collagen degradation; corneal ulcer.