title: Effects of exogenous recombinant human bone morphogenic protein-7 on the corneal epithelial mesenchymal transition and fibrosis.
abstract: OBJECTIVE
  To evaluate the effect of exogenous recombinant human bone morphogenic protein-7 (rhBMP-7) on transforming growth factor-β (TGF-β)-induced epithelial mesenchymal cell transition (EMT) and assessed its antifibrotic effectviatopical application.
  
  
  METHODS
  The cytotoxic effect of rhBMP-7 was evaluated and the EMT of human corneal epithelial cells (HECEs) was induced by TGF-β. HECEs were then cultured in the presence of rhBMP-7 and/or hyaluronic acid (HA). EMT markers, fibronectin, E-cadherin, α-smooth muscle actin (α-SMA), and matrix metaloproteinase-9 (MMP-9), were evaluated. The level of corneal fibrosis and the reepithelization rate were evaluated using a rabbit keratectomy model. Expression of α-SMA in keratocytes were quantified following treatment with different concentrations of rhBMP-7.
  
  
  RESULTS
  Treatment with rhBMP-7 attenuated TGF-β-induced EMT in HECEs. It significantly attenuated fibronectin secretion (31.6%;P<0.05), the α-SMA protein level (72.2%;P<0.01), and MMP-9 expression (23.6%,P<0.05) in HECEs compared with cells grown in the presence of TGF-β alone. E-cadherin expression was significantly enhanced (289.7%;P<0.01) in the presence of rhBMP-7. Topical application of rhBMP-7 combined with 0.1% HA significantly reduced the amount of α-SMA+cells by 43.18% (P<0.05) at a concentration of 2.5 µg/mL and by 47.73% (P<0.05) at 25 µg/mL, compared with the control group, without disturbing corneal reepithelization.
  
  
  CONCLUSIONS
  rhBMP-7 attenuates TGF-β-induced EMTin vitro, and topical application of rhBMP-7 reduces keratocyte myodifferentiation during the early wound healing stagesin vivowithout hindering reepithelization. Topical rhBMP-7 application as biological eye drops seems to be feasible in diseases involving TGF-β-related corneal fibrosis with corneal reepithelization disorders.
authors.affiliation: Department of Ophthalmology, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea.
authors.forename: Jin Kwon
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Eyegene Inc., Seoul 07528, Korea.
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Park
authors.affiliation: Eyegene Inc., Seoul 07528, Korea.
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Eyegene Inc., Seoul 07528, Korea.
authors.forename: Kwang Sung
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Eyegene Inc., Seoul 07528, Korea.
authors.forename: Yang Je
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Nune Eye Hospital, Seoul 06198, Korea.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: You
authors.affiliation: Cellumed. Co., Ltd., Seoul 08501, Korea.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Cellumed. Co., Ltd., Seoul 08501, Korea.
authors.forename: Ju Woong
authors.initials: JW
authors.lastname: Jang
authors.affiliation: Department of Ophthalmology, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Lee
keywords: bone morphogenic protein-7; corneal fibrosis; epithelial mesenchymal transition; myodifferentiation; transforming growth factor-β