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Effection Of Matrix Metalloproteinases And Their Inhibitors On Posterior Caupsular Opacification And Relation With Transforming Growth Factor-β2

Posted on:2003-05-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:N P DaiFull Text:PDF
GTID:1104360092990634Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
Posterior capsule opacification (PCO) is the commonest complication of extracapsular cataract extraction with an incidence of between 10% and 50% by 2 years postoperatively, and subsequently results in visual deterioration, but its mechanism of formation has not been understood completely. Histological and experimental studies suggest that residual lens epithelial cell proliferate, produce collagen and undergo fibrous, metaplasia in defective lens capsule after cataract surgery, resulting in secondary cataract. Extracellur matrix (ECM) including laminin, collagen, fibronectin and hyaluronic acid is the most important protein as structural components of cells, directing lens epithelial cell proliferation and migration, causing contraction and wrinkling of the lens capsule. The matrix metalloproteinases (MMPs) and their inhibitors are recognized as important enzymes both for normal extracellular matrix turnover and for exaggerated extracellular matrix breakdown associated with these pathologic conditions. Matrix metalloproteinases are zinc dependent proteinases that degrade compounds of the extracellular matrix. These enzymes play a pivotal role in turnover and remodeling of the ECM during organism growth and development and the pathological destruction of tissues in diseases. The activities of metalloproteinases are tightly controlled at several different transcriptive levels such as modulation bycytokines, growth factors and hormones. All MMPs are inhibited by their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), which are the multifunctional factors. TIMPs play a pivotal role in the regulation of ECM degradation remodeling. Physiologically, these TIMPs participate in tissue remodeling and maintaining normal tissue function, and pathokogically, they can inhibit MMPs activities causing disruption or disintegrtion of extracellular matrixces. Besides their inhibitory activities, the TIMPs play a role in growth-promotion and differentiation-promotion. Disruption of the balance between MMPs and TIMPs has been implicated in many diseases such as tumors invasion and metastasis.There have many growth factors and cytokines such as EGF (epithelial growth factor), bFGF (basic fibeoblast growth factor), TGF-β (transforming growth factor- β ), TNF- a (tumor necrosis factor- a ), IL-1 (interleukin-1) in aqueous humor after extracapsular cataract extraction, they are important in modulating the proliferiation of lens epithelial cells and the production of extracellular matrix, they also control the expression of MMPs and TIMPs. Cells, growth factors, cytokines, ECM and MMPs/TlMPs constitute the complicated networks dominating the dynamic balance of cells and ECM interaction. Once the network becomes disorganized, the pathological destruction of tissues will take place.Presently, the effections of MMPs and TIMPs on the formation of after-cataract have not reported. Our studies had operated extracapsular cataract extraction with intraocular lens implantation on the rabbit eyes, to investigate the dynamic changes of matrix metalloproteinases activity and their inhibitors, the formation of posterior capsular opacification and fibrosis in aqueous humor after cataract surgery by molecule-biology technology, to investigate the expression of MMPs and TIMPs mRNA and their proteinic tissue origins, to discuss further their relation with TGF- β2 to posterior capsular opacification and fibrosis.Part IDynamic Changes of MMPs, TIMPs and Hydroxyproline in Rabbit Eyes Aqueous Humor with Intraocular Lens ImplantationObjective : To investigate the changes of matrix metalloproteinases activity and their inhibitors in aqueous humor following intraocular lens implantation (IOL), and to expound the effects of MMPs and their inhibitors on the formation of posterior capsular opacification and fibrosis. Methods: Twenty-five adult rabbits were chosen in this study. In each rabbit, one eye underwent extracapsular cataract extraction (ECCE) with IOL and the other eye was normal. The aqueous humor samples...
Keywords/Search Tags:iris, LECs, MMPs, TIMPs, TGF-β, zymography, RT-PCR, posterior capsular opacification
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