TY - JOUR
T1 - Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction
AU - Okumura, Naoki
AU - Sakamoto, Yuji
AU - Fujii, Keita
AU - Kitano, Junji
AU - Nakano, Shinichiro
AU - Tsujimoto, Yuki
AU - Nakamura, Shin Ichiro
AU - Ueno, Morio
AU - Hagiya, Michio
AU - Hamuro, Junji
AU - Matsuyama, Akifumi
AU - Suzuki, Shingo
AU - Shiina, Takashi
AU - Kinoshita, Shigeru
AU - Koizumi, Noriko
PY - 2016/5/18
Y1 - 2016/5/18
N2 - 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.
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.
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U2 - 10.1038/srep26113
DO - 10.1038/srep26113
M3 - Article
C2 - 27189516
AN - SCOPUS:84970039350
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 26113
ER -