03189: Efficacy and Safety of Ripasudil and Nicotinamide for Canine Corneal Endothelial Dystrophy

One Health: Yes

Abstract

Corneal endothelial disease is a common condition that requires surgery in aged canine and human patients. The corneal endothelium maintains corneal clarity, which is critical for normal vision. In dogs, corneal endothelial dystrophy (CED) is a progressive disease in which the endothelial cells die resulting in corneal swelling and decreased vision. Corneal ulcers, infection, and perforation can also occur such that eye removal may be required.

In humans, corneal transplantation is commonly performed to treat a similar condition, Fuchs endothelial corneal dystrophy (FECD). However, corneal transplants are rarely performed in dogs due to the risk of graft rejection and lack of available donor tissue. Thus, medical treatments for canine CED and human FECD are urgently needed to reduce the requirement for surgery. The researchers’ laboratory has demonstrated that the drugs ripasudil and netarsudil, known as Rho Kinase or ROCK inhibitors, can delay the progression of CED in some - but not all - canine patients. Therefore, additional therapeutic strategies are needed to help all affected dogs.

Since oxidative stress and subsequent mitochondrial damage are known to be critical in the development of FECD, the investigators propose to utilize nicotinamide, an antioxidant that improves mitochondrial function, as a therapeutic for early CED. Previous studies in rabbits and mice demonstrated that nicotinamide accelerated corneal endothelial wound healing and protected the endothelium against ultraviolet B (UVB)-induced apoptosis. Nicotinamide is also safe in young, healthy dogs and available over the counter. Thus, the researchers expect that co-treatment with nicotinamide and ripasudil will delay progression of early CED and be well tolerated in older dogs. If successful, the results can be translated to human patients with FECD.