Schlemm’s canal targeted-Tie2 knockdown as a mouse model of adult-onset ocular hypertension and glaucoma

点击翻译按钮获取中文摘要

Glaucoma causes irreversible vision loss and blindness, but we still lack understanding of the multipart mechanisms that cause and drive glaucoma progression. Animal models enable investigation of cellular and molecular players throughout disease, and are essential for testing and optimizing new treatments. There is a need for animal models that selectively model pathogenic events of human glaucoma to trigger neurodegeneration with a predictable time of onset and progression. We have developed a mouse model that selectively disrupts Schlemm’s canal (SC) expression of Tie2, which is associated with ocular hypertension and glaucoma in humans. The studies proposed here will define the timecourse, sequence and variability of functional and structural optic nerve and RGC neurodegeneration in this model. We will also develop a CRISPR/Cas9 approach to disrupt Tie2 expression in SC, which could be applied independent of genetic background. This project is expected to provide an inducible glaucoma model relevant to study the pathogenesis of ocular hypertension and neurodegeneration, and a preclinical tool to evaluate new treatments for human glaucoma.