UW eye researchers publish second study of stem cells and blinding eye disease

August 25, 2015

Madison, Wisconsin – A team of eye researchers at the University of Wisconsin-Madison have used a custom stem cell model of a rare but blinding eye disease to test whether a commonly used drug might offer hope for treatment.

The study, “Pharmacological Modulation of Photoreceptor Outer Segment Degradations in a Human iPS Cell Model of Inherited Macular Degeneration,” was published in Molecular Therapy, the journal associated with The American Society of Gene and Cell Therapy. It focuses on applications of the basic sciences to therapeutics.

In 2012, the UW-Madison research team for the first time took skin cells from patients with Best disease, an inherited type of macular degeneration, and used induced pluripotent stem cells (iPSC) technology to turn them into retinal cells that mimicked the disease. This second study shows the next steps in the research.

David Gamm, MD, PhD
David Gamm, MD, PhD

Dr. David Gamm, the director of the McPherson Eye Research Institute and head of the lab that worked on the study, says there is no cure for Best disease, which causes slow loss of central vision. But the new study shows customized stem cells can be helpful to patients because they can be used to test the effects of drugs.

Best disease is often diagnosed in childhood while vision is still good, so there is ample time to intervene if an effective treatment to slow the disease can be identified.

“The study, which was led by Dr. Ruchira Singh, showed the application of the drug valproic acid was able to improve certain functions of retinal cells affected by Best disease,” said Gamm. “This stem cell model allowed us to learn about the disease before choosing specific drugs to test. We don’t expect drugs to reverse damage to retinal cells caused by Best disease, but they may slow it down.”

Samples from members of two families with Best disease were studied over the past three years. Children of affected individuals have a 50 percent chance of inheriting the causative gene.

Using samples from affected and unaffected siblings, they turned skin into stem cells, then into retinal pigment epithelium, the eye cells that are affected by this disease. Their studies suggest that a build-up of waste products due to a slower rate of protein digestion could play a role in the loss of central vision.

With the help of Drs. Karina Guziewicz and Gus Aguirre at the University of Pennsylvania, the paper also studied dogs that have a natural form of Best disease. While those tests showed encouraging trends, it was difficult to extrapolate to apply the findings to humans because dogs eliminate the drug much faster than humans.

“The big picture from this study and others is that human stem cells can be used for more than just transplantation,” said Gamm. “In this case we didn’t intend to place cells back into the patient’s eyes – instead, we re-created aspects of the disease in a dish to learn more about it and narrow down the types of drugs that might be helpful.”

Skin cells were used because the retinal cells needed for study cannot be biopsied without potentially blinding the patients further. Gamm says the critical next step is a clinical trial to see if valproic acid can one day be used as a treatment to help slow the progression of Best disease. Until then, the effect on patients will not be known.

“The individuals with advanced disease that volunteered for the study know that these types of treatments will not help their near term situation, but they are excited for the potential impact on future generations,” said Gamm. “Since there is no treatment option at present, the ability to generate stem cell models to test a variety of potential therapies is important. Plus, patients can partner with scientists in the process, which is empowering for them and tremendously helpful to us.”