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

Author

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  • Mingyu Yao

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Zhenhai Zeng

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Siheng Li

    (Chinese Academy of Medical Sciences
    Wenzhou Medical University)

  • Zhilin Zou

    (Wenzhou Medical University)

  • Zhongxing Chen

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Xinyi Chen

    (Wenzhou Medical University)

  • Qingyi Gao

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Guoli Zhao

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Aodong Chen

    (Wenzhou Medical University)

  • Zheng Li

    (Wenzhou Medical University)

  • Yiran Wang

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Rui Ning

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Colm McAlinden

    (Chinese Academy of Medical Sciences
    Queen Victoria Hospital)

  • Xingtao Zhou

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

  • Jinhai Huang

    (Chinese Academy of Medical Sciences
    Shanghai Research Center of Ophthalmology and Optometry)

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.

Suggested Citation

  • 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 & Jinhai Hua, 2024. "CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50050-4
    DOI: 10.1038/s41467-024-50050-4
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    References listed on IDEAS

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    1. Omar O. Abudayyeh & Jonathan S. Gootenberg & Patrick Essletzbichler & Shuo Han & Julia Joung & Joseph J. Belanto & Vanessa Verdine & David B. T. Cox & Max J. Kellner & Aviv Regev & Eric S. Lander & Da, 2017. "RNA targeting with CRISPR–Cas13," Nature, Nature, vol. 550(7675), pages 280-284, October.
    2. Yuancheng Lu & Benedikt Brommer & Xiao Tian & Anitha Krishnan & Margarita Meer & Chen Wang & Daniel L. Vera & Qiurui Zeng & Doudou Yu & Michael S. Bonkowski & Jae-Hyun Yang & Songlin Zhou & Emma M. Ho, 2020. "Reprogramming to recover youthful epigenetic information and restore vision," Nature, Nature, vol. 588(7836), pages 124-129, December.
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