C3 transferase-expressing scAAV2 transduces ocular anterior segment tissues and lowers intraocular pressure in mouse and monkey

Abstract 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 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.