Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension

Abstract

Summary: Glaucoma is one of the most common causes of irreversible blindness. It is acknowledged that lowering intraocular pressure (IOP) is the effective treatment to slow glaucoma disease progression. The main obstacle of existing drugs is that the effect of reducing IOP does not last long. Degradation of IκB stimulates the transcription of NF-κB, which could upregulate the expression of matrix metalloproteinases (MMPs). Whether a IκB-targeted gene therapy works in glaucoma is unclear. Here, we established a chronic ocular hypertension (COHT) model in rhesus monkey by laser photocoagulation and verified that intracameral delivery of IκBα-siRNA showed long-lasting and potent effects of reducing IOP without obvious inflammation in monkeys with COHT. We also verified that IκBα-siRNA could increase the expressions of MMP2 and MMP9 by knocking down IκBα in vitro and in vivo. Our results in nonhuman primates indicated that IκBα-siRNA may become a promising therapeutic approach for the treatment of glaucoma.

Keywords

• Biological sciences
• Cell biology
• Ophthalmology