Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction

Naoki Okumura, Yuji Sakamoto, Keita Fujii, Junji Kitano, Shinichiro Nakano, Yuki Tsujimoto, Shin Ichiro Nakamura, Morio Ueno, Michio Hagiya, Junji Hamuro, Akifumi Matsuyama, Shingo Suzuki, Takashi Shiina, Shigeru Kinoshita, Noriko Koizumi

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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.

Original languageEnglish
Article number26113
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 18-05-2016

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Okumura, N., Sakamoto, Y., Fujii, K., Kitano, J., Nakano, S., Tsujimoto, Y., Nakamura, S. I., Ueno, M., Hagiya, M., Hamuro, J., Matsuyama, A., Suzuki, S., Shiina, T., Kinoshita, S., & Koizumi, N. (2016). Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction. Scientific reports, 6, [26113]. https://doi.org/10.1038/srep26113