Abstract
ROCK (Rho kinase) signaling regulates a wide spectrum of fundamental cellular events and is involved in a variety of pathological conditions. It has therefore attracted research interest as a potential therapeutic target for combating various diseases. We showed that inhibition of ROCK enhances cell proliferation, promotes cell adhesion onto a substrate, and suppresses apoptosis of corneal endothelial cells (CECs). In addition, we reported that a ROCK inhibitor enhances wound healing in the corneal endothelium in animal models and in pilot clinical research. We also demonstrated the usefulness of a ROCK inhibitor as an adjunct drug in tissue engineering therapy as it enhances the engraftment of CECs onto recipient corneas. In 2013, we initiated a clinical trial to test the effectiveness of injection of cultured human CECs into the anterior chamber of patients with corneal endothelial decompensation. This paper reviews the accumulating evidence supporting the potency of ROCK inhibitors in clinical use, both as eye drops and as adjunct drugs in cell-based therapies, for the treatment of corneal endothelial decompensation.
Highlights
The corneal endothelium, through its pump-and-leak barrier functions, maintains corneal transparency by regulating the amount of water inside the corneal stroma
Any damage to the corneal endothelium is repaired by compensatory migration and spreading of the residual corneal endothelial cells (CECs) to cover the wounded area, with a resulting drop in the CEC density
Descemet’s stripping endothelial keratoplasty (DSEK) was introduced in the clinical setting in the last decade to reduce the invasiveness of penetrating keratoplasty and to improve clinical outcomes and is performed routinely worldwide, largely replacing penetrating keratoplasty
Summary
The corneal endothelium, through its pump-and-leak barrier functions, maintains corneal transparency by regulating the amount of water inside the corneal stroma. Any damage to the corneal endothelium is repaired by compensatory migration and spreading of the residual CECs to cover the wounded area, with a resulting drop in the CEC density. This density is typically 2000–2500 cells/mm in a normal subject, and a drop below a critical level, usually less than 500–1000 cells/mm, can result in a hazy cornea due to decompensation of the corneal epithelium. The evolution of surgical procedures has enabled less invasive treatment of corneal endothelial decompensation with better clinical outcomes These surgeries still have associated issues, such as the difficulty of the actual surgical technique, graft rejection, acute and chronic cell loss, and the shortage of donor corneas. This review provides an overview of the research into ROCK inhibitors and their potential for the clinical treatment of corneal endothelial decompensation
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