Patients' Skin Cells Help Researchers Move Closer to Treatments for Best Disease
Contrary to its name, Best disease is not a condition anyone wants. Named after the German ophthalmologist Friedrich Best more than a century ago, it is an inherited form of macular degeneration that can cause significant and progressive loss of central vision in children and adults.
But thanks to a newly developed human model of the disease — derived from the skin of two affected patients — researchers have a new tool to study the condition and help develop treatment approaches that might save vision. The research advancement was funded by the Foundation Fighting Blindness and posted today in the journal Human Molecular Genetics.
Dr. David Gamm, director of the McPherson Eye Research Institute at the University of Wisconsin-Madison, used an innovative technique to reprogram the patients’ skin cells into what are known as induced pluripotent stem cells, or iPSC. He then coaxed the iPSC forward to become retinal pigment epithelial (RPE) cells.
RPE cells play a critical supporting role in the retina, providing nutrition and waste disposal for photoreceptors, the cells that make vision possible. RPE cells are directly affected by Best disease, and when they become dysfunctional, photoreceptors in the central region of the retina known as the macula are progressively lost.
By studying the affected RPE cells in a dish, Dr. Gamm and his team were able to observe and understand critical elements of the disease process, including their ability to pump fluid which leads to the build-up of cysts. They also saw how the RPE cells did not effectively dispose of the tips of photoreceptors, which are shed every night during sleep. Additionally, the researchers noted that certain proteins — including rhodopsin, a pigment in photoreceptors that is critical for vision — were not being properly degraded by the RPE cells.
Studying Best disease in a laboratory dish using RPE cells derived from iPSC has many advantages and complements animal models of the condition. “It is a faster and less expensive process than using animal models,” Dr. Gamm says. “And, most important, it provides a human model of disease to help us understand how and why vision is lost in people. However, animal models remain essential in understanding disease and identifying potential cures, namely because they are a complete biological system.”
Dr. Gamm, a recent recipient of the Foundation’s Visionary Award, adds that the families’ perspectives on the research have been exciting for him. “One family came to my lab recently, and we spent an afternoon discussing their cells and their implications for them and their affected kids,” he says. “They are very happy to be involved in the research and our work toward treatments and cures.”
His laboratory is now using the families’ cells to evaluate potential vision-saving therapies.