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.

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.

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.

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.

We investigated the unfolding property and rotational stability of a new toric intraocular lens (IOL); TECNIS toric II (toric-II, ZCW, Johnson & Johnson) that is an improved version of TECNIS toric IOL (toric-I, ZCV). Both IOLs are based on an identical platform, except for the frosted haptics with toric-II IOL. The study consisted of two parts; experimental study and clinical, retrospective, case series. Experimental study indicated that the overall time from IOL ejection to unfolding to 11 mm was significantly shorter with toricII than toric-I IOLs (p = 0.032), due to the earlier separation of the haptics from the optic with toric-II IOL. Clinical study included 131 eyes of 99 patients who had undergone phacoemulsification and toric IOL implantation. At 3 months postoperatively, toric-II IOL showed significantly better rotational stability than toric-I IOL, including smaller residual manifest astigmatism (p = 0.018), less amount of axis misalignment from the intended axis (p = 0.04), lower incidence of misalignment > 10º (p = 0.0044), and less degree of prediction errors (p = 0.043). Postoperative uncorrected distance visual acuity tended to be better in the toric-II than in the toric-I groups, with marginal statistical difference (p = 0.057). TECNIS toric II IOL with the frosted haptics showed significantly better rotational stability than its predecessor, probably due to quicker unfolding and greater friction with the capsular bag.

No abstract

The corneal endothelium is essential for maintaining corneal transparency; therefore, corneal endothelial dysfunction causes serious vision loss. Tissue engineering-based therapy is potentially a less invasive and more effective therapeutic modality. We recently started a first-in-man clinical trial of cell-based therapy for treating corneal endothelial dysfunction in Japan. However, the senescence of corneal endothelial cells (CECs) during the serial passage culture needed to obtain massive quantities of cells for clinical use is a serious technical obstacle preventing the push of this regenerative therapy to clinical settings. Here, we show evidence from an animal model confirming that senescent cells are less effective in cell therapy. In addition, we propose that density-gradient centrifugation can eliminate the senescent cells and purify high potency CECs for clinical use. This simple technique might be applicable for other types of cells in the settings of regenerative medicine.