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.
North Carolina State University researchers have developed new technology designed to improve communication between dogs and humans.
Using their legs as sails and silk as anchors, spiders can travel on water to escape predators and colonize new habitats
Pigs ‘edited’ with a warthog gene to resist African swine fever could help spawn GM animal farms in the UK
Mouse House to make naturalist biopic, six years after box-office failure of Creation, starring Paul Bettany
International team spends 10 years making inroads into treatment of bacterium which kills up to half of those it infects
You may not know it, but you probably have some Neanderthal in you. For people around the world, except sub-Saharan Africans, about 1 to 3 percent of their DNA comes from Neanderthals, our close cousins who disappeared roughly 39,000 years ago.
Research at Yale plotted what happened in the brains of two scientists as they held a conversation
From medicines to jet fuel, we have so many reasons to celebrate the microbes we live with every day
Genome sequencing indicates Kennewick Man is Native American, reopening the bitter battle over whether he should be reburied or studied
In the article on the discovery of dinosaurs (They’re back, Review, 6 June) you state: “In Sussex, a local doctor uncovered fragmentary remains of what appeared to be two more species of colossal extinct land reptiles.” You grossly underplay the contribution of Lewes-born Gideon Mantell, geologist and palaeontologist, author and diarist, friend to princes and international scholars as well as local doctor. Mantell not only discovered (aided by his wife) the first remains of the iguanodon in 1824 but named it – as it resembled the tooth of an iguana. This was the first known land dinosaur, Mary Anning having identified the first sea-living dinosaur.Mantell went on to put together more pieces of the jigsaw with extra fossil discoveries. In contrast to Richard Owen, whose models form the basis for the Crystal Palace dinosaurs, Mantell stated correctly that iguanodon would have walked on their back legs, using their forearms to fight or gather food. He did, however, attribute the thumb spike to a nose horn though later corrected this assumption. The Natural History Museum has a display on Gideon and his wife Mary’s contribution as well as the large “Mantell-piece” of Iguanodon fossils that he had on show in his museum in Brighton. He sold it, along with many more priceless items, to the British Museum in 1838. Gideon Mantell’s reputation deserves better than your throwaway remark. Debby MatthewsLewes, East Sussex Continue reading...