Gaining more hen-sight into Lebers Congenital Amaurosis

"We were able to restore function to the photoreceptor cells in the retinas of an avian model of a disease that is one of the more common causes of inherited blindness in human infants," said Sue Semple-Rowland, Ph.D., an associate professor of neuroscience with UF's Evelyn F. and William L. McKnight Brain Institute. "The vision capabilities of the treated animals far exceeded our expectations."
The bird -- a type of Rhode Island Red chicken -- carries a genetic defect that prevents it from producing an enzyme essential for sight. The condition closely models a genetic disease in humans that causes Leber congenital amaurosis type 1, or LCA1. About 2,000 people in the United States are blind because they have a disease that falls in the LCA family.

"Enabling chickens that can't see to peck and eat after treatment is stunning," said Dr. Jean Bennett, a professor of ophthalmology and cell and developmental biology at the University of Pennsylvania who was not involved in the study but who participated in a landmark gene transfer experiment five years ago that restored vision to blind Briard dogs. "This is proof of concept using a unique vector, animal model and approach. One would hope this could happen in a human."
Semple-Rowland, a College of Medicine faculty member, has worked since 1986 to first discover the malfunctioning gene, known as GC1, and then to develop a viral therapy to treat it.

Later, more precise tests showed that of the seven treated chickens, five displayed near-normal visual behavior. Measurement of electrical activity in the retinas of the same five animals showed they responded to light. In comparison, tests on three untreated chickens showed no meaningful responses.

"This is an interesting gene-transfer technique that appears to restore function to light-sensitive cells in the retina," said Dr. Paul A. Sieving, director of the National Eye Institute of the National Institutes of Health, which partially funded the study. "An approach such as this could lead eventually to a vision-restoring therapy for children who suffer from blinding retinal diseases."
Like people, chickens possess color vision and function best in daylight. The predominant photoreceptor cell type in the chicken retina, the cone cell, is the same cell type that is essential for normal human vision.

To develop the treatment, UF scientists constructed a virus able to infect photoreceptors, delivering a normal copy of the GC1 gene to these cells. Using a very fine glass needle, they injected the viral vector into the developing nervous system of a chicken embryo through a tiny hole in the eggshell. The shell was resealed and the egg was incubated to hatching to produce a live chick.

Infants with LCA1 would receive an injection of the gene transfer agents directly into the eyeball during the first couple of years of life, bypassing embryonic treatment. That's important, researchers say, because a diagnosis of LCA1 is often not made until months after a child is born.

Work remains to refine the viral delivery system that transfers the healthy genes to the photoreceptor cells. In addition, solutions have to be found to make the treatment long-lasting -- scientists have restored sight and slowed degeneration, but the retinal cells still degenerate.

But Semple-Rowland thinks the time necessary to turn these research results into a treatment for patients will be a fraction of the 20 years that have gone into discovering the genetic defect and developing a therapy for it.

"We can do amazing things in animal models," Semple-Rowland said, "but this work can't be done quickly. That's the hardest thing -- knowing there are people who need these treatments now. But we work as fast as we can. You'll see the first treatments for some of these genetic eye diseases soon, especially after the groundwork for an approved therapy is laid and the therapy works."

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