Impression And Its Significance Of Metalloproteinases In Crush Wound Of Rat Optic Nerve

Purposes: The response of the axon to injury is a vital area of research as new approaches are developed to enhance the regeneration of optic nerve. Matrix metalloproteinases, a group of proteinases, the main contributors of extracellular matrix degradation, participate in the most of the physiological and pathological processes involved in cell migration, proliferation, and matrix remodeling. It is assumed that metalloproteinases play a critical role in wound healing process. This study aims to evaluate the possible roles of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) in the crush wound of optic nerve.Materials and Methods: Firstly, rat model was induced by means of incompletely crush wound of optic nerve using across action forceps at 2mm behind eyeball.Then we oberserved the injury of axon by both anterograde and retrograde tracing of FluoroGold; used the method of gelatin zymography to detected levels of MMP-2 and MMP-9 and further to defined it by Western blotting; then detected the exist of mRNA of MMP-2 and MMP-9 by RT-PCR; revealed the MMPs was spatially correlated with scar formationan and possible function by in situ zymograph and immunohistochemistry.Results: 57% of RGCs remained alive and the distant axon decreased at 2 weeks, neovascularization and chondroitin sulfate proteoglycan(CSPG) was observed at injury site as the negative components of regeneration. MMP-2 and MMP-9 were found to be transiently upregulated in the crush optic nerve, MMP-2 exists in the both normal optic nerve and crush optic nerve. MMP-9 was only detected in the crush wound group. The mRNA of MMP-9 was only detected in the wound optic nerve. MMPs distributions are at the edge of injury site, and the local levels of CSPG are often inversely correlated with gelatinase activity levels.Conclusions: The poor regeneration of optic nerve is partially related with neovascularization and CSPG deposit of injury site. MMP-2 and MMP-9 were involved in the pathological process of crush optic nerve.The possible function of MMPs is degrading the CSPG and benefiting for optic nerve regeneration.The expression of mRNA of MMP-2 and MMP-9, indicates the glial cells may be a candidate of secretion in the optical nerves.