A New Direction

On June 10, 2014, M. Valeria Canto-Soler, PhD, The Johns Hopkins University School of Medicine, caught the attention of the entire medical research world when she and collaborators announced that they had created miniature human retinas in a dish that not only had the architectural organization of a human retina but also the ability to sense light. It was the culmination of a career change five years in the making—one that started with financial support from RPB.

This project has required significant financial investment. The continuous support from RPB has been essential for its success.

"My research focuses on the mechanisms that regulate the behavior of retinal cells in both normal and diseased conditions," says Canto-Soler, Director of the Retinal Degenerations Research Center at Wilmer Eye Institute. "In 2009, I wanted to start a completely new line of cutting-edge research. I was fortunate to be able to use funds from RPB's Unrestricted Grant [to the department of ophthalmology] to incorporate the use of human induced pluripotent stem cells (iPSCs) in my work. That support, literally, launched a whole new direction in my career."

Her training in this new field took Dr. Canto-Soler and her post-doctoral fellow, Dr. Xiufeng Zhong, to the lab of David Gamm, MD, PhD, and Director of the McPherson Eye Research Institute at the University of Wisconsin School of Medicine and Public Health. Gamm, who received an RPB Nelson Trust Award in 2014 as well as an RPB/IRRF Catalyst Award, is recognized as a pioneer in directing iPSCs into becoming retinal cells.

"We spent two weeks there, learning the techniques that we took back to our lab," she recalls. "Funds from RPB supported that critical visit as well. To this day, Dr. Gamm and I maintain a dynamic communication and frequently discuss potential projects."

The skills and techniques she acquired with RPB support, coupled with her lab's successes, helped her to receive additional grants from government sources. "We knew that if we were to reproduce the functional characteristics of the retina we would have to recreate its complex, three-dimensional cellular structure," explains Canto-Soler. "But when we began this work, we had no idea if our iPSCs would be able to form a retina, almost on their own. Somehow the cells knew what to do."

That was their first, pleasant surprise. They were equally surprised when the cells responded to light stimulus. "The element of the unknown in science can be humbling," she adds. "While our mini retinas may respond to light, we do not know if they are capable of producing a signal that the brain can interpret as an image. That may take quite some time yet."

To expand her work on the retina-in-a-dish system, her department chair nominated Canto-Soler for an RPB Special Scholar Award, which she received in 2013.

"We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," says RPB Special Scholar Awardee Dr. Valeria Canto-Soler, Johns Hopkins University School of Medicine. In the long term, these structures could be used to study the causes of retinal diseases, to test drugs tailored to individual patients, and possibly to replace diseased or dead retinal tissue.

"These mini retinas develop at the same pace as human embryonic retinas. A three-month-old retina-in-a-dish has developed to the same extent as a retina at three months of gestation. The system allows us, for the first time, to study healthy retinal development as it occurs. We can also introduce retinal disease gene mutations in order to study the steps and mechanisms in the development of human retinal diseases, such as retinitis pigmentosa and Stargardt's."

One of the goals with these studies is to develop a platform for patient-specific screening of drugs that could have a clinical application. Eventually, the Canto-Soler lab hopes to recreate in these mini retinas a level of maturation such that lab-grown retinal tissue transplantation would be feasible.

"An RPB grant makes it possible for a researcher to switch direction not only mid-investigation, but also, as in my case, mid-career. This is profoundly liberating. All of us in vision science are aware of the high quality of the researchers who receive RPB grants and of the rigorous approval process that takes place there. I think I am not alone when I say that, if you receive a grant from RPB, you feel that your work is of value to the vision research community. This gives you a sense of self-assurance and added motivation."

June 9, 2015