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Abstract #81133 Published in IGR 20-3
Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys
Tan J; Liu G; Zhu X; Wu Z; Wang N; Zhou L; Zhang X; Fan N; Liu XMolecular Therapy 2019; 27: 1327-1338
Primary open-angle glaucoma (POAG) is considered a lifelong disease characterized by optic nerve deterioration and visual field damage. Although the disease progression can usually be controlled by lowering the intraocular pressure (IOP), therapeutic effects of current approaches do not last long. Gene therapy could be a promising method for persistent treatment of the disease. Our previous study demonstrated that gene transfer of exoenzyme C3 transferase (C3) to the trabecular meshwork (TM) to inhibit Rho GTPase (Rho), the upstream signal molecule of Rho-associated kinase (ROCK), resulted in lowered IOP in normal rodent eyes. In the present study, we show that the lentiviral vector (LV)-mediated C3 expression inactivates RhoA in human TM cells by ADP ribosylation, resulting in disruption of the actin cytoskeleton and altered cell morphology. In addition, intracameral delivery of the C3 vector to monkey eyes leads to persistently lowered IOP without obvious signs of inflammation. This is the first report of using a vector to transduce the TM of an alive non-human primate with a gene that alters cellular machinery and physiology. Our results in non-human primates support that LV-mediated C3 expression in the TM may have therapeutic potential for glaucoma, the leading cause of irreversible blindness in humans.
Xiamen Eye Center, Xiamen University, Xiamen, China; Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, School of Optometry, Shenzhen University, Shenzhen, China.
Full articleClassification:
11.9 Gene therapy (Part of: 11 Medical treatment)
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
