文章基本信息

标题：Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension
本地全文：下载
作者：Difang Sun ; Zongyi Zhan ; Rui Zeng 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-21
DOI：10.1016/j.isci.2022.104149
语种：English
出版社：Elsevier
摘要：SummaryGlaucoma 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 IκBαin vitroandin vivo. Our results in nonhuman primates indicated that IκBα-siRNA may become a promising therapeutic approach for the treatment of glaucoma.Graphical abstractDisplay OmittedHighlights•Knocking down IκBα could upregulate the expression of MMP2 and MMP9 in MCM and MTM•LP could induce COHT model in rhesus monkeys successfully•IκBα-siRNA has a long-term and potent IOP-lowering effect in LP-induced monkeys with COHTBiological sciences; Cell biology; Ophthalmology