Combined effects of interleukin-1β and cyclic stretching on metalloproteinase expression in corneal fibroblasts in vitro.

Pengfei Feng,Shuo Rong,Weiyi Chen,Xiaona Li,Genlai Du,Xiaojun Wang,Chengxing Liu

doi:10.1186/s12938-016-0198-6

Pengfei Feng, Shuo Rong + Show 5 more

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https://doi.org/10.1186/s12938-016-0198-6

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Abstract

BackgroundCorneal tensile strain increases if the cornea becomes thin or if intraocular pressure increases. However, the effects of mechanical stress on extracellular matrix (ECM) remodelling in the corneal repair process and the corneal anomalies are unknown.MethodsIn this study, the combined effects of interleukin-1β (IL-1β) on matrix metalloproteinases (MMPs) in corneal fibroblasts under cyclic stretching were investigated in vitro. Cultured rabbit corneal fibroblasts were subjected to 5, 10 or 15 % cyclic equibiaxial stretching at 0.1 Hz for 36 h in the presence of IL-1β. Conditioned medium was harvested for the analysis of MMP2 and MMP9 protein production using the gelatin zymography and western blot techniques.Results and conclusionsCyclic equibiaxial stretching changed the cell morphology by increasing the contractility of F-actin fibres. IL-1β alone induced the expression of MMP9 and increased the production of MMP2, and 5 % stretching alone decreased the production of MMP2, which indicates that a low stretching magnitude can reduce ECM degradation. In the presence of IL-1β, 5 and 10 % stretching increased the production of MMP2, whereas 15 % stretching increased the production of MMP9. These results indicate that MMP expression is enhanced by cyclic mechanical stimulation in the presence of IL-1β, which is expected to contribute to corneal ECM degradation, leading to the development of post-refractive surgery keratectasia.

Highlights

Corneal tensile strain increases if the cornea becomes thin or if intraocular pressure increases
Pro-matrix metalloproteinase 2 (MMP2) produced by cells treated with 0.4 and 0.8 ng/mL IL-1β are Cyclic stretching alone had a bidirectional effect on Pro‐MMP2 and further increased Pro‐MMP2 and Pro‐matrix metalloproteinase 9 (MMP9) in the presence of IL‐1β After 36 h of cyclic equibiaxial stretching, Pro-MMP2 and Pro-MMP9 in the cell supernatant were determined
Corneal fibroblasts were subjected to combined cyclic stretching and IL-1β to determine the effect of mechanical strain on corneal extracellular matrix (ECM) metabolism

Summary

Introduction

Corneal tensile strain increases if the cornea becomes thin or if intraocular pressure increases. Corneal refractive surgery is one of the most widely used methods for the correction of refractive errors [1]. The distribution of stress or strain in the cornea under intraocular pressure (IOP) was investigated. Animal experiments [2,3,4] and finite element simulation [5, 6] show that corneal membrane stress or strain increases after keratorefractive surgery. As a load-bearing tissue, the cornea is mainly subjected to biaxial tensile stress because of IOP in vivo [7]. The combination of tight eye closure and forceful rubbing may increase the IOP to more than 10 times the normal levels, perhaps even higher [11].

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