UW Eye Research Institute
Studies of Drosophila, the common fruit fly, are providing insights into
mechanisms of retinal degeneration in human diseases such as macular degeneration
and retinitis pigmentosa.
“The pursuit of genetic mutations that cause retinal degenerations is not unlike assembling an airplane,” says Nansi Colley, associate professor of Ophthalmology and Visual Sciences and Genetics, and member of the UW Eye Research Institute. “In some diseases, genetic mutations remain unknown. In others, the mutations are known but how they cause disease is not. Unraveling the underlying mechanism of disease is complex because, unfortunately, we don't have the 'assembly plans' for humans.”
Originally trained as a marine biologist and geneticist, Dr. Colley investigates a creature far removed from sea life—Drosophila, the common fruit fly. Just as the Cessna is a miniature relative of a 747, the fruit fly serves as a small-scale model to provide clues about how the human visual system works in health and disease. In Dr. Colley's lab, the flies are the cornerstones of work on understanding blinding diseases such as macular degeneration and retinitis pigmentosa.
“Drosophila are ideal organisms for unraveling the genetic basis of a disease,” says Dr. Colley. “A single mating produces 150 offspring that are genetically identical. Fruit flies have a two-month lifespan, so we can study the onset and progression of an age-related disease in a very short time. And, best of all, we already have the parts list — the entire genetic makeup of the fruit fly is well known. We can therefore identify the genetic mutations and study the mechanisms leading to vision loss.”
Diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are genetically diverse, meaning that different families likely have varying genetic causes for the disease. This variability makes it challenging for the ophthalmologist to diagnose any one individual’s disease. Dr. Colley’s lab is focused on gathering information about the genetics of AMD and RP through the eye of the fly. Information gathered through the fruit fly model will help physicians treat these difficult conditions in their patients.
Her task began with a screening of 12,000 different sets of fruit flies that had been exposed to a chemical causing genetic mutations. Of that group, over 900 were observed to undergo retinal degenerations; each of these 900 mutations holds the potential for inroads to therapeutic treatments. But how to choose which to pursue first?
Dr. Colley’s lab further characterized the pathology and underlying cell biology and biochemistry of these degenerations and set out to map the genes defined by the mutations. She focused first on a major visual pigment in the retina, known as rhodopsin. A key cause of vision loss in RP is due to mutations in rhodopsin; in fact, over 100 mutations in the rhodopsin molecule have already been identified in human patients with blinding disease.
Retinal degenerations can be triggered by defects in almost every protein involved in the light-converting pathways of the eye, and two common mechanisms involve protein folding defects and unregulated calcium levels. ...(Next) (Previous)