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 Jou*, I. Jong Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1345-1357
Number of pages13
JournalJournal of Molecular Medicine
Volume97
Issue number9
DOIs
StatePublished - 1 Sep 2019

Keywords

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

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