Researchers from Penn’s School of Veterinary Medicine have used gene therapy to cure day blindness in dogs—a groundbreaking advance that may help researchers one day restore day sight in humans, as well.

Clinician scientist András M. Komáromy, assistant professor of ophthalmology at Penn Vet and lead author of the study, worked with a team from the University, Temple, the University of Florida and Cornell to restore sight to dogs suffering from achromatopsia, also known as rod monochromacy or total color blindness. This disease affects the cones in the eye, and is rare—affecting about 1 in 30,000 to 50,000 humans—but is a perfect model to study all diseases that impair the cones. The cones in eyes are responsible for color vision and most daily activities, including reading.

“Several diseases affect the cones and when the cones are lost, that’s when patients become severely affected and their quality of life deteriorates,” says Komáromy. “We know achromatopsia, as an example, primarily affects the cones and is a perfect model for understanding diseases in cones.”

In fact, studying achromatopsia may even help researchers understand how to fight age-related macular degeneration, the leading cause of blindness in people more than 60 years old.

“If you can figure out how to treat these cones,” Komáromy adds, “we may be able to slow down vision loss or even prevent vision loss.”

As a veterinary ophthalmologist, Komáromy is keenly interested in inherited eye diseases in dogs. He says canines make excellent models for studying these diseases because the structure and size of dogs’ eyes are similar to that of humans. Plus, dogs are easy to train and are much easier to work with than some other animal models. “Our work benefits both dogs and humans,” says Komáromy. “It can be translated and ... the jump from the dog to the human is not as big as some [other animals].”

Komáromy worked on the study with Gustavo D. Aguirre, professor of medical genetics and ophthalmology, and Jessica Rowlan, a research specialist. In 2001, Aguirre and his team were the first to restore vision in blind dogs using gene therapy. That work restored vision to Lancelot, a Swedish briard dog born with Leber’s congenital amaurosis, or LCA, a rare genetic defect. In their current work, Komáromy says they have gone a step further with gene therapy, treating cells that are responsible for vision and absorption of light.

While Komáromy’s findings are a breakthrough, he says there are mysteries yet to uncover. One, for instance, is why the gene therapy cured day blindness in younger dogs, but had a reduced success rate in canines more than a year old. “That’s something that we need to tackle,” he says. “We’re working on ways to see if we can convert cones into a more immature state and then do the gene therapy.”

The researcher is optimistic about what this therapy means for canines—and for humans—even though much work needs to be done to monitor long-term results, potential complications and toxicity.

Clinical trials are in the not-too-distance future. According to Komáromy, “I think it’s fairly realistic to think that within five years, [this will] enter Phase 1 clinical trials in human patients.”

To watch a video of dogs with no vision problems and dogs with vision problems navigate a simple maze, go to www.upenn.edu/pennnews/current/latestnews/042110.html.

Originally published May 6, 2010