Stem Cells Form Light-Sensitive 3-D Retinal Tissue

Induced pluripotent stem cells form a structure with layers of cells, including photoreceptors (red). Image by the researchers, courtesy of Nature Communications

Researchers induced human stem cells to create a 3-D retina structure that responds to light. The finding may aid the study of eye diseases and could eventually lead to new therapies.

When we view a sunset or a soccer game, an intricate, orchestrated series of events takes place in our eyes. Light passes through the front part of each eye and is refracted and focused on the retina, a thin, delicate tissue at the back of our eyes. The retina contains many specialized cells, including photoreceptor cells, which convert light into electrical signals. These signals are then processed and sent to the brain. If the photoreceptor cells malfunction or die, vision loss and blindness can occur.

Researchers have previously shown that induced pluripotent stem (iPS) cells can grow into a type of retinal cell under certain cell culture conditions. These types of stem cells are adult cells that have been genetically reprogrammed to take on the characteristics of embryonic stem cells. They can grow indefinitely in the laboratory and can theoretically change, or differentiate, into all cell types found in the body.

Previous work showed that mouse and human embryonic stem cells can develop into a 3-D optic cup in culture that resembles the embryonic vertebrate eye. A team led by Drs. Xiufeng Zhong and M. Valeria Canto-Soler at Johns Hopkins University set out to determine to what extent iPS cells could be prompted to differentiate and acquire structural and functional features similar to a human retina. The work was funded in part by NIH’s National Eye Institute (NEI) and National Heart, Lung, and Blood Institute (NHLBI).

The scientists grew human iPS cells in culture dishes in the lab. They reported online on June 10, 2014, in Nature Communications that they were able to coax the cells to gradually take on the characteristics of retinal cells without adding many of the chemicals typically used to induce the cells to mature.

Over time, the iPS cells spontaneously formed cup-like 3-D structures in a sequence of events that mimicked what occurs during human development. The structures developed layers containing all the major cell types that are normally present in the retina, including photoreceptor cells.

To determine whether the photoreceptor cells were sensitive to light, the researchers subjected cells to a flash of light and measured the electrical responses in individual cells. A few cells responded, indicating they had reached a fairly advanced stage of development under the culture conditions.

“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,” Canto-Soler says. “When we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do.”

The accomplishment may lead to better tissue culture models to study human eye diseases and explore new therapies.

—by Carol Torgan, Ph.D.