Research restores vision to blind mice: Fort Worth physician engineers skin cells into retinal cells

FORT WORTH, Texas  – Researchers have found a way to enable blind mice to be able to detect light by reprogramming skin cells into eye cells.

The study’s lead investigator, in the newly published study in Nature, is Sai Chavala, M.D., a professor at the TCU and UNTHSC School of Medicine in Fort Worth.

“I am thrilled to be a part a team of extremely talented and dedicated researchers. Our field of medicine (Ophthalmology) is a bit underrepresented in scientific research, and there are few studies related to vision that are published in Nature magazine every year. To have one of these come from our research lab is a true honor.”

In the report, lead author Dr. Chavala, who is also the CEO and president of CIRC Therapeutics and the Center for Retina Innovation as well as the director of retina services at KE Eye Centers of Texas, laid out this novel  approach to retinal regeneration that skirts the need for stem cells. The study was funded by the National Eye Institute (NEI) and the research was conducted at the North Texas Eye Research Institute at the University of North Texas Health Science Center at Fort Worth (HSC).  The Health Science Center owns the intellectual property and has licensed rights for commercial development to CIRC Therapeutics.

“The excitement with stem cells is that they can form essentially any cell in the body,” Dr. Chavala said. “But the problem from a clinical standpoint is that they can become any cell in the body by growing rapidly. So how do you know that when you put these cells into the retina (eye) that you don’t accidentally inject a stem cell that can form a tumor?”

The technique the team discovered directly reprograms skin cells into light-sensing rod photoreceptors without a stem cell intermediary step, that can take six months or longer before cells or tissues are ready for transplantation. In comparison, the researchers’ lab-made rods only took 10 days to become ready for transplantation. It enabled blind mice to detect light after the cells were transplanted into the animal’s eye.  Dr. Chavala and his team also demonstrated that they can reprogram human skin cells into retinal cells.

By producing retina-like cells, the study shows that there are new and faster approaches to developing therapies for patients with the most common form of age-related  macular degeneration and other retinal disorders caused by the loss of photoreceptors.

“Our technique goes directly from skin cell to photoreceptor (eye cell) without the need for stem cells in between,” Dr. Chavala said. “The idea is that one day we might be able to offer a personalized treatment for macular degeneration by surgically transplanting one’s own engineered skin cells into the retina to serve as photoreceptor-like cells and hopefully restore vision.”

The breakthrough is important because currently, researchers have only been able to restore vision in patients with wet (neovascular) macular degeneration. Wet macular degeneration is characterized by blood vessels that grow under the retina and leak, which is rare and typically happens suddenly.

However, the more common form of vision loss is dry macular degeneration, which happens over the course of years. Dry macular degeneration is common among people 50 and older and causes blurred or reduced central vision due to thinning of the macula, which is the part of the retina responsible for clear vision in your direct line of sight.“For that form (dry) of macular degeneration there is no therapy. There is no treatment,” Dr. Chavala said. “It’s frustrating for me because patients come to the clinic looking for hope and we’ve got nothing to offer. You’ve got people who have worked 30-40 years and are ready to enjoy retirement and then all of a sudden you get dry macular degeneration and you can’t see.  I was inspired to become a physician-scientist to try to solve this problem.”

As a faculty member, Dr. Chavala’s scientific breakthrough is also meaningful to the medical students he teaches at the TCU and UNTHSC School of Medicine, who are exposed to the interface of research and medicine.

“Dr. Chavala’s work represents a significant advancement in the worldwide challenge to address retinal disease and blindness,” said Stuart Flynn, M.D., the Founding Dean of the TCU and UNTHSC School of Medicine. “This work is a wonderful model for our students as they learn and experience the robust interface between the science and art of medicine, always with the focus on the patient”

And for patients regularly visiting Dr. Chavala’s clinic in North Texas, like Keller resident Roy Ryan, 88, finding a cure for dry macular degeneration would mean a lot for him and countless others.

“We’re hopeful that the cure is coming soon and if not for me for future generations to come,” Ryan said.

The next step for Dr. Chavala and his team of researchers will be working toward Federal Drug Administration approval, which is anticipated to be a 2 to 3-year process if adequate funding can be obtained, before the eye cell treatment can be studied in a clinical trial. Further research is needed to optimize the protocol to increase the rate of transplanted photoreceptors becoming functional.  Dr. Chavala and his team have made strides to develop this technology to benefit patients with glaucoma.

“Vision loss is all about quality of life and that’s extremely important.” Dr. Chavala said. “I want my patients and the public to know that there is hope in sight.”

Moving forward, HSC will continue to support Dr. Chavala’s startup company and his efforts to seek further funding and development toward commercialization.

“We have world class research going on in Fort Worth at the Health Science Center,” said Claude Longoria, HSC Director of Technology Commercialization. “Our objective is to identify promising technology and help advance innovative technologies to benefit patients.”

Prescotte Stokes III is the Integrated Content and Marketing Manager. You can reach him at p.stokes@tcu.edu