For the first time, Wisconsin researchers have taken skin from patients and, using induced pluripotent stem cell (iPSC) technology, turned them into a laboratory model for an inherited type of macular degeneration.
Dr. David Gamm, director of the UW's McPherson Eye Research Institute, said that while Best disease is relatively rare, having a patient-specific model of the eye disease, which destroys the macula of the retina, could lead to a greater understanding of more common eye disorders such as age-related macular degeneration.
"This model gives us a chance to understand the biological effects of human gene mutations in a relatively expeditious manner,'' says Gamm, associate professor of ophthalmology and visual sciences and pediatrics. "Ultimately, we hope the model will help us craft treatments to slow or reverse the course of Best Disease."
Gamm and lead researchers Dr. Ruchira Singh and Dr. Wei Shen, all members of the UW's Waisman Center, took skin samples from members of two Chicago-area families with Best disease.
Children in those families have a 50-percent chance of inheriting the gene that causes the disease, which begins destroying the macula as early as age three. Using samples of affected and unaffected siblings, they turned the skin into stem cells, then into retinal pigment epithelium, the cells of the eye that are affected by the disease.
In the laboratory dish, they were able to track the changes that underlie a lesion on the retina that resembles "egg yolk," and progresses to a stage called "scrambled egg," which destroys the central vision.
The UW model revealed some of the cellular processes causing the disease. The models of the Best disease patients showed a buildup of fluid and old photoreceptor cells, indicating something gone wrong with the ability to degrade and remove debris such as dead cells. On a molecular level, the Best cells were slow to degrade rhodopsin, a biological pigment in photoreceptor cells, and had differences in calcium signaling and oxidative stress.
"These results give us some ideas where to look for therapies that would allow us to interfere with the disease process,'' says Gamm. "And the stem cell model gives us a chance to test those therapies before trying them on patients."
Even more important, on a human level, is how excited some of the family members were to participate in understanding and eventually treating a disease that has plagued generations of their families.
"These family members know they're not getting treated directly as a result of this study, but they're doing it out of concern for the next generation,'' Gamm said. "That brings peace to them, to know that they're not passive victims of this disease, but instead, active players in the discovery process."
The chief research officer of the Foundation Fighting Blindness, which helped fund the Best disease project, says the method holds promise for a number of retinal conditions.
"We are delighted by the highly innovative research of Dr. Gamm and his lab in harnessing stem cells to better understand complex retinal diseases and move us closer to vision-saving treatments and cures,'' says Dr. Stephen Rose. "His techniques can be used to help characterize and overcome the entire spectrum of inherited retinal conditions."
The study on a model for Best disease is being published online today in the journal Human Molecular Genetics.
University of Wisconsin-Madison: http://www.wisc.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
When you’re the size of a human, you worry about lions and tigers and bears. But if you’re …
An amateur fossil hunter has unearthed a 7ft skeleton of a carnivorous marine reptile on a beach in south Wales.
European regulators have recommended approval of the first medicine containing stem cells to treat a rare condition caused by burns to the eye.
Ecologists say birds could hear the oncoming storm from over 100 miles away
Marine scientists plumbing the deepest part of the ocean sent microphones and collection probes baited with chicken to the bottom of a trench near Guam. Now they watch, wait ... and listen.
Lead author of two retracted papers resigns her position after failing to reproduce new approach to generating stem cells
The winners of the 2014 Olympus BioScapes Digital Imaging Competition capture a rat brain, the mouthparts of a vampire moth and other small wonders
By analysing brain activity linked to hand and arm movements, a team has created a robotic arm that a paralysed woman can control with her thoughts
Adding laser tips to ordinary shoes can improve the stride and pace of people with Parkinson's disease
Technique could someday help repair injuries