PMID- 27189516
OWN - NLM
STAT- MEDLINE
DCOM- 20180327
LR  - 20220321
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 May 18
TI  - Rho kinase inhibitor enables cell-based therapy for corneal endothelial 
      dysfunction.
PG  - 26113
LID - 10.1038/srep26113 [doi]
LID - 26113
AB  - The corneal endothelium maintains corneal transparency; consequently, its 
      dysfunction causes severe vision loss. Tissue engineering-based therapy, as an 
      alternative to conventional donor corneal transplantation, is anticipated to 
      provide a less invasive and more effective therapeutic modality. We conducted a 
      preclinical study for cell-based therapy in a primate model and demonstrated 
      regeneration of the corneal endothelium following injection of cultured monkey 
      corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a 
      Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also 
      evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade 
      HCECs, similar to those planned for use as transplant material for human patients 
      in a clinical trial, and we showed that the corneal endothelium was regenerated 
      without adverse effect. We also showed that CEC engraftment is impaired by 
      limited substrate adhesion, which is due to actomyosin contraction induced by 
      dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK 
      inhibitor improves efficiency of engraftment of CECs and enables cell-based 
      therapy for treating corneal endothelial dysfunction as a clinically relevant 
      therapy.
FAU - Okumura, Naoki
AU  - Okumura N
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
FAU - Sakamoto, Yuji
AU  - Sakamoto Y
AD  - Research Laboratory, Senju Pharmaceutical Co., Ltd., Kobe, Japan.
FAU - Fujii, Keita
AU  - Fujii K
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
FAU - Kitano, Junji
AU  - Kitano J
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
FAU - Nakano, Shinichiro
AU  - Nakano S
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
FAU - Tsujimoto, Yuki
AU  - Tsujimoto Y
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
FAU - Nakamura, Shin-Ichiro
AU  - Nakamura S
AD  - Research Center of Animal Life Science, Shiga University of Medical Science, 
      Otsu, Japan.
FAU - Ueno, Morio
AU  - Ueno M
AD  - Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, 
      Japan.
FAU - Hagiya, Michio
AU  - Hagiya M
AD  - Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, 
      Japan.
FAU - Hamuro, Junji
AU  - Hamuro J
AD  - Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, 
      Japan.
FAU - Matsuyama, Akifumi
AU  - Matsuyama A
AD  - Platform of Therapeutics for Rare Disease, National Institutes of Biomedical 
      Innovation, Health and Nutrition, Osaka, Japan.
FAU - Suzuki, Shingo
AU  - Suzuki S
AD  - Department of Molecular Life Science, Division of Basic Medical Science and 
      Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
FAU - Shiina, Takashi
AU  - Shiina T
AD  - Department of Molecular Life Science, Division of Basic Medical Science and 
      Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
FAU - Kinoshita, Shigeru
AU  - Kinoshita S
AD  - Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, 
      Japan.
AD  - Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Koizumi, Noriko
AU  - Koizumi N
AD  - Department of Biomedical Engineering, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160518
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Cell Transplantation/*methods
MH  - Cells, Cultured
MH  - Corneal Diseases/*therapy
MH  - Disease Models, Animal
MH  - Endothelial Cells/*physiology
MH  - Humans
MH  - Macaca fascicularis
MH  - Protein Kinase Inhibitors/*administration & dosage
MH  - Treatment Outcome
MH  - rho-Associated Kinases/*antagonists & inhibitors
PMC - PMC4870691
COIS- Shigeru Kinoshita obtained a patent regarding the application of ROCK inhibitor 
      for corneal endothelium (registration number: 5657252). N. O. and N. K. are 
      listed as inventors of the patent.
EDAT- 2016/05/18 06:00
MHDA- 2018/03/28 06:00
PMCR- 2016/05/18
CRDT- 2016/05/19 06:00
PHST- 2016/01/06 00:00 [received]
PHST- 2016/04/27 00:00 [accepted]
PHST- 2016/05/19 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2018/03/28 06:00 [medline]
PHST- 2016/05/18 00:00 [pmc-release]
AID - srep26113 [pii]
AID - 10.1038/srep26113 [doi]
PST - epublish
SO  - Sci Rep. 2016 May 18;6:26113. doi: 10.1038/srep26113.