Two rat models of glaucoma were used to study molecular changes taking place in the retina after an induction of high intraocular pressure (IOP). In the first model, high IOP is induced by a cauterization of two episcleral veins. This model was established in the laboratory. In the second model, the degeneration of the optic nerve is induced by an injection of concentrated saline solutions into the episcleral vein (a collaboration with Dr. J. Morrison, Casey Eye Institute). It has been demonstrated that the level of Myoc/Tigr mRNA is down regulated in the retina in both models of glaucoma. This reduced level of Myoc/Tigr mRNA can not be explained by ganglion cell death alone, since the level of this mRNA is up-regulated after the optic nerve transection which leads to pronounced ganglion cell death. The regulation of the Myoc/Tigr gene was studied in transfection experiments and in transgenic animals. The E-box element, which is critical for the activity of the human Myoc/Tigr promoter, was identified. Mutations in this element dramatically decreased promoter activity in vitro. The mouse Myoc/Tigr promoter (-2250/+51) was active in the photoreceptor cells of the retina and in the tissues of the eye angle of the transgenic mice. The antiserum, which was raised against the N-terminal part of the mouse Myoc/Tigr protein, was used to analyze the distribution of this protein in the mouse eye and other mouse tissues. It has been shown that Myoc/Tigr protein is more abundant in the tissues of the eye angle, sclera and cornea, than in other tissues analyzed. cDNA arrays were used to study changes in gene expression in the retina after high IOP induction. Several genes changing their expression have already been identified. The role of these genes in the glaucoma progression is now analyzed. cDNA libraries were constructed from rat retina and eye angle tissues (trabecular meshwork, iris and ciliary body). About 20 new cDNAs were identified in these libraries.
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