2. Academic Validation
  3. Targeting non-muscle myosin II promotes corneal endothelial migration through regulating lamellipodial dynamics

Targeting non-muscle myosin II promotes corneal endothelial migration through regulating lamellipodial dynamics

  • J Mol Med (Berl). 2019 Sep;97(9):1345-1357. doi: 10.1007/s00109-019-01818-5.
Wei-Ting Ho 1 2,  Jung-Shen Chang 3,  San-Fang Chou 4,  Wei-Lun Hwang 5,  Po-Jen Shih 6,  Shu-Wen Chang 1 7,  Muh-Hwa Yang 8 9,  Tzuu-Shuh Jou 10 11 12,  I-Jong Wang 13 14
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
  • 2 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 3 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
  • 4 Department of Medical Research, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
  • 5 Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
  • 6 Department of Civil and Environmental Engineering, National University of Kaohsiung, Kaohsiung, Taiwan.
  • 7 College of Medicine, National Taiwan University, No. 7, Chung-Shan S. Rd., Taipei, Taiwan.
  • 8 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
  • 9 Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 10 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. [email protected].
  • 11 College of Medicine, National Taiwan University, No. 7, Chung-Shan S. Rd., Taipei, Taiwan. [email protected].
  • 12 Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. [email protected].
  • 13 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. [email protected].
  • 14 College of Medicine, National Taiwan University, No. 7, Chung-Shan S. Rd., Taipei, Taiwan. [email protected].
PMID: 31302714 DOI: 10.1007/s00109-019-01818-5
Abstract

Corneal endothelial cell (CEC) dysfunction causes corneal edema that may lead to blindness. In addition to corneal transplantation, simple descemetorhexis has been proposed to treat centrally located disease with adequate peripheral cell reserve, but promoting the centripetal migration of CECs is pivotal to this strategy. Here, we show that targeting non-muscle Myosin II (NMII) activity by Y27632, a ROCK Inhibitor, or blebbistatin, a selective NMII inhibitor, promotes directional migration of CECs and accelerates in vitro wound healing. The lamellipodial protrusion persistence is increased, and actin retrograde flow is decreased after NMII inhibition. Counteracting lamellipodial protrusion by actin-related protein 2/3 (ARP2/3) inhibitor abolishes this migration-promoting effect. Although both Y27632 and blebbistatin accelerate wound healing, cell junctional integrity and barrier function are better preserved after blebbistatin treatment, leading to more rapid corneal deturgescence in rabbit corneal endothelial wounding model. Our findings indicate that NMII is a promising therapeutic target in the treatment of CEC dysfunction. KEY MESSAGES: NMII inhibition promotes directional migration and wound healing of CECs in vitro. Lamellipodial protrusion persistence is increased after NMII inhibition. Selective NMII inhibitor preserves junctional integrity better than ROCK Inhibitor. Selective NMII inhibitor accelerates corneal deturgescence after wounding in vivo.

Keywords

Cell migration; Corneal endothelial cell; Lamellipodia; Non-muscle myosin II; Wound healing.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13813
    99.64%, Myosin II Inhibitor