Naoki Okumura

I have been developing both pharmaceutical and tissue engineering treatment for corneal endothelial dysfunction. The corneal endothelium is critical for maintaining homeostatic corneal transparency, which it accomplishes by pump and barrier functions. When corneal endothelial cell density decreases to a critical level, the cornea exhibits haziness, with edema, due to decompensation of the corneal endothelial function.

We showed that a Rho-associated kinase (ROCK) inhibitor can be useful in treating corneal endothelial dysfunction. In 2009, we demonstrated that the selective ROCK inhibitor, Y-27632, showed unique effects on cultured CECs: 1) promotion of proliferation; 2) enhancement of cell adhesion; and 3) suppression of apoptosis. Our subsequent studies revealed that administration of ROCK inhibitors in the form of eye drops promotes CEC proliferation in rabbit and monkey in vivo models. In addition to animal experiments, we have started a clinical trial of ROCK inhibitor eye drops in combination for treatment of human corneal endothelial dysfunction patients.

We also demonstrated that in rabbit and monkey corneal endothelial dysfunction models, corneal transparency was restored via the injection of cultivated CECs with the selective ROCK inhibitor into the anterior chamber. One technical obstacle that currently exists is the difficulty of the in vitro expansion of CECs, as they exhibit fibroblastic phenotypes with loss of pump and barrier functions while under the culture conditions. However, we successfully established a CEC culture protocol for clinical use. This protocol enables the efficient in vitro expansion of CECs and may ultimately provide clinicians with a new therapeutic modality in regenerative medicine. Of note, our team has started the first in man clinical trial of cultivated CEC-injection therapy in Japan.