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

青光眼导致不可逆转的视力丧失和失明，但我们仍然缺乏对其各个部分的了解 导致和推动青光眼进展的机制。动物模型能够研究细胞和 分子在疾病中的作用，对于测试和优化新的治疗方法是必不可少的。有一个 需要选择性模拟人类青光眼致病事件的动物模型来触发 神经退行性变具有可预测的发病和进展时间。我们已经开发出一种老鼠模型， 选择性干扰Schlemm管(SC)Tie2的表达，与高眼压有关 以及人类的青光眼。这里提出的研究将定义时间进程、顺序和变异性 功能和结构视神经及RGC神经退行性变。我们还将开发一种 CRISPR/Cas9方法阻断Tie2在SC中的表达，该方法可以独立于基因应用 背景资料。该项目有望提供一种诱导性青光眼模型，用于研究 高眼压和神经退行性变的发病机制和临床前评估新疗法的工具 治疗人类青光眼。

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.