title: Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.affiliation: Research Laboratory, Senju Pharmaceutical Co., Ltd., Kobe, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kitano
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakano
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tsujimoto
authors.affiliation: Research Center of Animal Life Science, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Hagiya
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Koizumi
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D003316:Corneal Diseases / Q000628:therapy*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases