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

  • Wei-Ting Ho
  • Jung-Shen Chang
  • San-Fang Chou
  • Wei-Lun Hwang
  • Po-Jen Shih
  • Shu-Wen Chang
  • Muh-Hwa Yang
  • Tzuu-Shuh JouEmail author
  • I-Jong WangEmail author
Original Article

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

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

Notes

Acknowledgments

We are grateful to the Microscopy Core Facility, Department of Medical Research, National Taiwan University Hospital and National Taiwan University Molecular Imaging Center for providing the instrumentation for this study. We also thank Ms. Yung-Ching Wang for technical support.

Funding information

This study is supported by funding from the Taiwan Ministry of Science and Technology (MOST 105-2628-B-418-001-MY3 and MOST 107-3017-F-002-002) and TVGH-NTUH Joint Research Program (VN105-1, VN106-05, and VN107-15).

Compliance with ethical standards

Use of animal and the experimental procedures were in accordance with the principles of the Association for Research in Vision and Ophthalmology Statement for Use of Animals in Ophthalmic and Vision Research and were approved by the Institutional Animal Care and Use Committee of the National Taiwan University Hospital.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyFar Eastern Memorial HospitalNew Taipei CityTaiwan
  2. 2.Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of OphthalmologyNational Taiwan University HospitalTaipeiTaiwan
  4. 4.Department of Medical ResearchFar Eastern Memorial HospitalNew Taipei CityTaiwan
  5. 5.Department of Biotechnology and Laboratory Science in MedicineNational Yang‐Ming UniversityTaipeiTaiwan
  6. 6.Department of Civil and Environmental EngineeringNational University of KaohsiungKaohsiungTaiwan
  7. 7.College of MedicineNational Taiwan UniversityTaipeiTaiwan
  8. 8.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan
  9. 9.Division of Medical Oncology, Department of OncologyTaipei Veterans General HospitalTaipeiTaiwan
  10. 10.Center of Precision Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan

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