CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice

Mingyu Yao, Zhenhai Zeng, Siheng Li, Zhilin Zou, Zhongxing Chen, Xinyi Chen, Qingyi Gao, Guoli Zhao, Aodong Chen, Zheng Li, Yiran Wang, Rui Ning, Colm McAlinden, Xingtao Zhou () and Jinhai Huang ()
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Mingyu Yao: Chinese Academy of Medical Sciences
Zhenhai Zeng: Chinese Academy of Medical Sciences
Siheng Li: Chinese Academy of Medical Sciences
Zhilin Zou: Wenzhou Medical University
Zhongxing Chen: Chinese Academy of Medical Sciences
Xinyi Chen: Wenzhou Medical University
Qingyi Gao: Chinese Academy of Medical Sciences
Guoli Zhao: Chinese Academy of Medical Sciences
Aodong Chen: Wenzhou Medical University
Zheng Li: Wenzhou Medical University
Yiran Wang: Chinese Academy of Medical Sciences
Rui Ning: Chinese Academy of Medical Sciences
Colm McAlinden: Chinese Academy of Medical Sciences
Xingtao Zhou: Chinese Academy of Medical Sciences
Jinhai Huang: Chinese Academy of Medical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

Date: 2024
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DOI: 10.1038/s41467-024-50050-4

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