Glaucoma is a lifelong disease with elevated intraocular pressure (IOP) as the main risk factor, and reduction of IOP remains the major treatment for this disease. However, current IOP-lowering therapies are far from being satisfactory. We have demonstrated that the lentivirus-mediated exoenzyme C3 transferase (C3) expression in rat and monkey eyes induced relatively long-term IOP reduction. We now show that intracameral injection of self-complementary AAV2 containing a C3 gene into mouse and monkey eyes resulted in morphological changes in trabecular meshwork and IOP reduction. The vector-transduced corneal endothelium and the C3 transgene expression, not vector itself, induced corneal edema as a result of actin-associated endothelial barrier disruption. There was a positive (quadratic) correlation between measured IOP and grade of corneal edema. This is the first report of using an AAV to transduce the trabecular meshwork of monkeys with a gene capable of altering cellular structure and physiology, indicating a potential gene therapy for glaucoma.

中文翻译：

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表达C3转移酶的scAAV2转导小鼠和猴子的眼前节组织并降低眼内压。

青光眼是一种终生疾病，其眼内压升高（IOP）是主要危险因素，而降低IOP仍是该疾病的主要治疗方法。但是，目前降低眼压的疗法远不能令人满意。我们已经证明，慢病毒介导的外切酶C3转移酶（C3）在大鼠和猴眼中的表达诱导了相对长期的IOP降低。我们现在显示向小鼠和猴眼前房内注射含有C3基因的自互补AAV2会导致小梁网和IOP减少的形态变化。由于肌动蛋白相关的内皮屏障破坏，载体转导的角膜内皮和C3转基因表达（而不是载体本身）诱导角膜水肿。测得的眼压和角膜浮肿程度之间存在正相关（二次相关）。