Primary open angle glaucoma and corticosteroid induced glaucoma are common clinical problems in intraocular pressure is elevated due to trabecular outflow obstruction. The site of increased resistance to the outflow of the aqueous humor in these disorders, is thought to be the juxtacanalicular extracellular matrix of the trabecular meshwork. We hypothesize that a class of enzymes, the matrix metalloproteinases, are important in regulating the extracellular matrix and consequently in controlling aqueous humor outflow. We have demonstrated the ability of interleukin 1alpha to induce changes in the trabecular levels of these enzymes. The approach of this proposal is to use interleukin 1alpha, dexamethasone and related reagents to further explore the possible effects of cytokines on the matrix metalloproteinase. We asses these effects using both human and porcine cell culture, organ culture and perfused organ culture. Zymograms, immunohistochemistry, in-situ hybridization and western immunoblots with supplementation by polymerase chain reaction will be used to asses the effects of cytokines, their natural inhibitor and related reagents on the trabecular meshwork. Changes in metalloproteinase levels will then be correlated with changes in aqueous humor outflow rates in a perfused explant organ culture model. Studies on the effect of interleukin 1alpha and dexamethasone on trabecular extracellular matrix may help us to understand how corticosteroids cause and increase in intraocular pressure. Our findings may suggest therapeutic agents to treat open angle glaucomas by enhancing outflow in the eye.
| Alexander, J P; Samples, J R; Acott, T S (1998) Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression. Curr Eye Res 17:276-85 |
