Glucocorticosteroids are known to cause intraocular pressure (IOP) elevation in susceptible individuals that can lead to glaucomatous optic neuropathy. Steroid-induced glaucoma resembles primary open angle glaucoma in the mechanism of IOP elevation and in the optic neuropathy. Some of the cellular & molecular mechanisms leading to IOP elevation have been studied in tissue and/or organ culture but not in vivo. Thus, a reliable animal model of steroid-induced glaucoma would be extremely valuable as an in vivo system for testing specific hypotheses about these mechanisms. We have found that IOP significantly increases in bovine eyes treated topically with corticosteroids for more than 4 weeks. The consistency of the steroid response in this species, together with the size of the bovine eye and its similarities to the human eye make it an ideal animal model for steroid-induced glaucoma. As the first steps towards establishing the suitability of this model for future studies, we propose an investigation to achieve the following 3 specific aims: 1. To determine the histopathological changes that occur in major structures associated with glaucoma (TM, retina and optic nerve head (ONH)) during the course of steroid-induced IOP elevation in the bovine eye and to determine the correlation of each change with the level and duration of IOP elevation. ? 2. To generate cDNA libraries of differentially expressed genes in the TM, retina and ONH at various time points during the steroid-induced IOP elevation. Such libraries will be screened in the future for novel genes that are involved in steroid-induced IOP elevation as well as genes that may be involved in the response of the retina and ONH when IOP is elevated by corticosteroids. 3. To determine differentially expressed genes in the TM, retina and ONH at specific time points during the steroid-induced IOP elevation using microarrays. Determination of these changes will allow us to potentially determine the sequence of molecular events responsible for the development of glaucomatous pathology. ? ? ?
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