UF Discovery Of Chicken Gene Mutation Aids Study Of Rare Inherited Eye Disease

July 22, 1998

GAINESVILLE — A University of Florida neuroscientist has discovered and cloned a mutant gene in chickens, helping researchers better understand a rare human eye disease that causes blindness at birth.

Sue Semple-Rowland, an associate professor of neuroscience in UF’s College of Medicine and the UF Brain Institute, has established a specific type of the Rhode Island Red chicken as the animal model for studying the human disease, called Leber’s congenital amaurosis type I, or LCA-I. She will present her work Thursday at the Eighth International Symposium on Retinal Degeneration in Schluchsee, Germany.

“The way the retina works is similar in chickens and humans, so I think it is reasonable to assume that what we develop in this lab for the chicken will be something that could be very useful in treating people,” Rowland said.

Rowland now is developing a form of gene therapy for chickens with the disease.

“The eye offers a unique opportunity to employ gene therapy because it is a closed system,” she said. “The cells in the eye are highly specialized for the work they do, which enables us to better target them for gene therapy.”

LCA-I is among the earliest and most severe forms of autosomal recessive inherited retinal degeneration. Autosomal recessive diseases occur when a person receives a defective copy of a particular gene from both parents.

The retina, a light-sensitive tissue at the back of the eye, contains photoreceptors called rods and cones. The receptors convert light into electrical and chemical signals, which are then sent to visual centers in the brain through the optic nerve. In people with LCA-I and in the retinal-degeneration chicken, the defective guanylate cyclase gene fails to make a protein needed for this basic visual process.

Cones, the receptors that enable color vision, are essential for human sight. Chicken eyes have a high percentage of cones, which makes them excellent models for studying human eye diseases.

Inherited retinal diseases affect 100,000 to 200,000 people in the United States and more than 1 million worldwide. While only one to three people in 100,000 suffer from LCA, scientists speculate that successful gene therapy for this disease may be helpful in developing treatments for other autosomal recessive diseases, such as cystic fibrosis.

Rowland has published several papers on her research, most recently in the February issue of the Proceedings of the National Academy of Sciences. A $1.1 million grant from the National Institutes of Health supports her research, and she has applied for a new NIH grant to further fund the gene therapy study.

Rowland is collaborating with Krzysztof Palczewski of the University of Washington, Wolfgang Baehr of the Moran Eye Center at the University of Utah Health Science Center, and Lung-Ji Chang, an associate professor of molecular genetics and microbiology in UF’s College of Medicine.

Three other UF College of Medicine researchers also are presenting their work at the retinal degeneration symposium. Bill Hauswirth, the Rybaczki-Bullard eminent scholar of ophthalmology and molecular genetics and microbiology, and Al Lewin, a professor in the department of molecular genetics and microbiology, will present information on AAV gene therapies for retinal diseases. Paul Hargrave, the Francis N. Bullard eminent scholar of ophthalmology and biochemistry and molecular biology, will present some of his most recent work on the visual pigment protein, rhodopsin. Hargrave has shown how mutations in this protein cause certain forms of inherited eye disease.