We have recently identified key structural similarities between aqueous humor outflow in mouse eyes, including a well-defined uveoscleral outflow pathway, and human eyes. We also have developed novel methods for measuring aqueous humor dynamics in the mouse, and discovered that they also have similar physiological characteristics to humans. Moreover, we have shown that mouse intraocular pressure, like human intraocular pressure, is reduced by topical administration of a widely-used prostaglandin analogue (latanoprost), and that latanoprost increases uveoscleral outflow in the mouse eye. These similarities indicate that the mouse eye is highly suitable for studying biologic mechanisms influencing intraocular pressure and how it changes under different conditions. Our technical advances now enable us to use transgenic mice to ascertain how activating or altering specific genes influences intraocular pressure.
Specific Aim 1. To determine age-related changes in intraocular pressure, conventional outflow, uveoscleral outflow, and prostaglandin-mediated pressure lowering in normal and transgenic mice with abnormal collagen metabolism.
Specific Aim 2. To determine prostaglandin-mediated alterations of scleral matrix metalloproteinase gene transcription, protein biosynthesis, and transscleral-permeability in vitro and in vivo.
Specific Aim 3. To determine the role of specific signal transduction events in the intraocular pressure lowering and aqueous dynamics changes induced by topical prostaglandin treatment of mouse eyes. The results of these studies have important implications for the discovery of new treatments for glaucoma and other vision-threatening eye diseases.
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