Programm                 "Degeneration und Regeneration– Grundlagen, Diagnostik und Therapie"


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Abstract
Abstract

Amelioration of experimental autoimmune uveitis with a selective gelatinase inhibitor through inhibition of MMP-dependent chemotaxis

Walch A., Ardjomand N., El-Shabrawi Y. 
Universitäts-Augenklinik Graz/A

Purpose: The chemotaxis of inflammatory cells toward the inflamed site depends on proteolytic disruption of extracellular matrix components and is a major factor in every immune response. Secretion of proteolytic active MMP-2 and-9 enables transmigrating T-lymphocytes to pass through the subendothelial basement membrane en route to the perivascular tissue. Inhibiting this step in the immune response was at the heart of this study.
Method: An oligo-petide that selectively blocks MMP-2 and -9 was generated. Its ability to prevent the digestion of extracellular matrix components by lymphocytes as well as its effect on the chemotaxis of lymphocytes through an artificial basement membrane was tested using enzyme inhibition assays and lymphocyte migration assays. Further the antiinflammatory effect of this synthetic MMP inhibitor was evaluated in a model of experimental autoimmune uveitis.
Results: Using the selective MMP-2 and -9 inhibitor reduced or almost completely abolished the ability of lymphocytes to digest type I collagen. The chemotaxis of lymphocytes through an artificial basement membrane was reduced by up to 40%. In our in-vivo model, experimental autoimmune uveitis, in the group that was treated with the selective MMP-inhibitor 7 of 13 animals (53 %), versus 12/ 12 in control group developed EAU. The mean activity of the disease wa


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