IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50050-4.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50050-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50050-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. David N. Fiflis & Nicolas A. Rey & Harshitha Venugopal-Lavanya & Beatrice Sewell & Aaron Mitchell-Dick & Katie N. Clements & Sydney Milo & Abigail R. Benkert & Alan Rosales & Sophia Fergione & Aravind, 2024. "Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Zhifang Li & Ruochen Guo & Xiaozhi Sun & Guoling Li & Zhuang Shao & Xiaona Huo & Rongrong Yang & Xinyu Liu & Xi Cao & Hainan Zhang & Weihong Zhang & Xiaoyin Zhang & Shuangyu Ma & Meiling Zhang & Yuanh, 2024. "Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Evan A. Schwartz & Jack P. K. Bravo & Mohd Ahsan & Luis A. Macias & Caitlyn L. McCafferty & Tyler L. Dangerfield & Jada N. Walker & Jennifer S. Brodbelt & Giulia Palermo & Peter C. Fineran & Robert D., 2024. "RNA targeting and cleavage by the type III-Dv CRISPR effector complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Yage Ding & Cristina Tous & Jaehoon Choi & Jingyao Chen & Wilson W. Wong, 2024. "Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Jamie L. Endicott & Paula A. Nolte & Hui Shen & Peter W. Laird, 2022. "Cell division drives DNA methylation loss in late-replicating domains in primary human cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Xiangyu Deng & Emmanuel Osikpa & Jie Yang & Seye J. Oladeji & Jamie Smith & Xue Gao & Yang Gao, 2023. "Structural basis for the activation of a compact CRISPR-Cas13 nuclease," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Xiaolong Cheng & Zexu Li & Ruocheng Shan & Zihan Li & Shengnan Wang & Wenchang Zhao & Han Zhang & Lumen Chao & Jian Peng & Teng Fei & Wei Li, 2023. "Modeling CRISPR-Cas13d on-target and off-target effects using machine learning approaches," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Duško Lainšček & Vida Forstnerič & Veronika Mikolič & Špela Malenšek & Peter Pečan & Mojca Benčina & Matjaž Sever & Helena Podgornik & Roman Jerala, 2022. "Coiled-coil heterodimer-based recruitment of an exonuclease to CRISPR/Cas for enhanced gene editing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Ali Doğa Yücel & Vadim N. Gladyshev, 2024. "The long and winding road of reprogramming-induced rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    11. Breanna DiAndreth & Noreen Wauford & Eileen Hu & Sebastian Palacios & Ron Weiss, 2022. "PERSIST platform provides programmable RNA regulation using CRISPR endoRNases," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    12. Huaxia Shi & Ying Xu & Na Tian & Ming Yang & Fu-Sen Liang, 2022. "Inducible and reversible RNA N6-methyladenosine editing," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Amanda R. Krysler & Christopher R. Cromwell & Tommy Tu & Juan Jovel & Basil P. Hubbard, 2022. "Guide RNAs containing universal bases enable Cas9/Cas12a recognition of polymorphic sequences," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    14. Antonios Apostolopoulos & Naohiro Kawamoto & Siu Yu A. Chow & Hitomi Tsuiji & Yoshiho Ikeuchi & Yuichi Shichino & Shintaro Iwasaki, 2024. "dCas13-mediated translational repression for accurate gene silencing in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Feiyu Zhao & Tao Zhang & Xiaodi Sun & Xiyun Zhang & Letong Chen & Hejun Wang & Jinze Li & Peng Fan & Liangxue Lai & Tingting Sui & Zhanjun Li, 2023. "A strategy for Cas13 miniaturization based on the structure and AlphaFold," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    16. Noemie Vilallongue & Julia Schaeffer & Anne-Marie Hesse & Céline Delpech & Béatrice Blot & Antoine Paccard & Elise Plissonnier & Blandine Excoffier & Yohann Couté & Stephane Belin & Homaira Nawabi, 2022. "Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    17. Pei Liu & Josquin Foiret & Yinglin Situ & Nisi Zhang & Aris J. Kare & Bo Wu & Marina N. Raie & Katherine W. Ferrara & Lei S. Qi, 2023. "Sonogenetic control of multiplexed genome regulation and base editing," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    18. Lauren A. Blake & Leslie Watkins & Yang Liu & Takanari Inoue & Bin Wu, 2024. "A rapid inducible RNA decay system reveals fast mRNA decay in P-bodies," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Hongrui Zhao & Yan Sheng & Tenghua Zhang & Shujun Zhou & Yuqing Zhu & Feiyang Qian & Meiru Liu & Weixue Xu & Dengsong Zhang & Jiaming Hu, 2024. "The CRISPR-Cas13a Gemini System for noncontiguous target RNA activation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    20. M. Alejandra Zeballos C. & Hayden J. Moore & Tyler J. Smith & Jackson E. Powell & Najah S. Ahsan & Sijia Zhang & Thomas Gaj, 2023. "Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50050-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.