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.

Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery.

These findings show that ROCK inhibitors employ both cyclin D and p27 via PI 3-kinase signaling to promote CEC proliferation, and that Y-39983 may be a more potent agent than Y-27632 for facilitating corneal endothelium wound healing.

ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage to prevent progression of bullous keratopathy. (University Hospital Medical Information Network Clinical Trial Registry no. UMIN000003625; www.umin.ac.jp/ctr).

Purpose: To compare the incidence of re-orientating surgery to improve misalignment of three models of acrylic toric intraocular lenses: AcrySof toric intraocular lens (Alcon Laboratories, Inc.), TECNIS toric intraocular lens (Johnson & Johnson Vision, Inc.) and HOYA 355 toric intraocular lens (HOYA). Methods: In this retrospective, multicenter case series, medical charts were reviewed for collecting data on realignment surgery of toric intraocular lenses at 10 ophthalmic surgical sites in Japan. Results: Over all, intraocular lens repositioning surgery was conducted in 89 of 9430 eyes (0.944%) at an average of 10.5 ± 9.7 days after the initial cataract surgery. The incidence was 0.213% (11/5155), 1.797% (62/3451) and 1.942% (16/824) with AcrySof, TECNIS and HOYA toric intraocular lenses, respectively. The incidence was significantly lower with AcrySof than with other two brands of toric intraocular lenses ( p < 0.0001). In those eyes which underwent reorientation surgery, the amount of misalignment was 26.4 ± 21.9°, 29.7 ± 15.4° and 28.1 ± 20.7° with AcrySof, TECNIS and HOYA toric intraocular lenses, respectively; there was no significant difference among groups ( p = 0.821). The repositioning surgery significantly reduced misalignment in all three groups. Conclusion: The rotational stability was considerably different among toric intraocular lenses of different manufacturers. The incidence of repositioning surgery was significantly lower with AcrySof than with TECNIS and HOYA toric intraocular lenses.