| Background and Aim As a common complication to rhegmato- genous retinal detachment (RRD) and surgery of it, proliferative vitreoretinopathy (PVR) is the leading cause of anatomical failure in retinal detachment surgery. PVR may be viewed as a maladapted wound healing phenomenon which involved many kinds of inflammatory cytokines and growth factors. Inflammative response is initiative factor in PVR and retinal pigment epithelium(RPE) is major proliferative cells in PVR process. In quiescent state, the RPE basement membrane tightly adheres to Bruch's membrane. However, at the beginning of PVR process, stimulated and activated by the initiative factors, RPE begin to dislocate from Bruch's membrane , migrate, proliferate, dedifferentiate, transdifferentiate and secrete provisinal extracellular matrix proteins, followed by membrane formation and contraction on both surfaces of the neuroretina and in the vitreous body, resulted in tractional retinal detachment.Matrix metalloproteinases (MMPs) are a family of zinc binding, calcium-dependent endopeptidases that are expressed by various tissues and cell types and function by degrading extracellular matrix (ECM)components. Having lots of biological function, MMPs are involved in normal physiological and pathologic processes, such as degradation of basement membrane, remodeling of ECM, regulation of cell adhesiveness, initiation of potential cellular function via interaction of extracellular protein components, connective tissue turnover, angiogenesis, reproduction, embryogenesis and wound repair. As the nature tissue inhibitor of MMPs, TIMPs can prevent activation of the latent pro-MMPs and inhibit activity of MMPs. In addition, TIMPs present growth factors-like activity and can modulate cell proliferation and apoptosis. Therefore, the imbalance of MMPs/TIMPs ratio can result in tumor progression and metastasis, rheumatic arthritis, etc al.It was reported that the expression of MMPs and TIMPs in PVR membrane, and inflammatory cytokines can upregulate MMPs/TIMPs ratio expressed in cultured human RPE. Here we investigated (1) the expression of MMPs and TIMPs in PVR membrane; (2) the expression of MMPs and TIMPs in the migratory cells from cultured membranes obtained during surgery; (3)whether IL-1B and TNF-a could upregulate the MMPs and TIMPs activity and mRNA level, and if so, whether IL-1rA, genistein, dexamethasone could abolish the increase of them induced by IL-1B and TNF-a; (4) whether the intracellular calcium level changed in RPE during migration in a denuding model; as well as whether IL-ip, TNF-a, IL-lrA, genistein, dexamethasone could influence the calclium level. Methods (1) Sections of epiretinal membrane from 31 PVR patients were stained by immunohistochemistry to investigate the expression of MMP-2,9 and TIMP-1,2 and by ISH of MMP-2mRNA. The ultrastructure of PVR membranes were observed by transmission electronic microscopy(TEM). (2) Surgical excised membranes from patients with PVR were cultured to detect the expression of MMP-2, 9 and TIMP-1,2 in migratory cells from culturedmembranes. (3) Human RPE cells were cultured from eye bank donor eyes. The activity of MMP-2,9 were detected in RPE by zymography incubated with or without IL-1B and TNF-a, as well as combined with or without IL-1rA, genistein and dexamethasone respectively. The secreted MMP-2 level in cultured hRPE medium were measured by ELISA. The mRNA levels of MMP-2, 9 and TIMP-1, 2 were examined by RT-PCR incubated with or without IL-1B and TNF-a, as well as combined with or without IL-lrA, genistein and dexamethasone respectively. (4) A small area of a confluent monolayer of human RPE cells was denuded with a cotton bud to create wound healing model in vitro. After incubated with IL-1B and TNF-a, or combined with or without neutralizing IgG of anti-human MMP-2, IL-lrA, genistein and dexamethasone respectively, the regulation of migration efficiency was measured as the number of cells that had entered the denuded area. The calcium level of migratory RPE cell...
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