With their eyes on the possibility of finding treatment for human eye diseases, two researchers began their work.

Don Sakaguchi and Michael Young first met in 1997 on the island of Crete at a scientific meeting dealing with the development of the brain. About two years later, the men combined their efforts to begin paving the way for future treatment in diseases of the human eye.

Both researchers were familiar with each other’s work: Sakaguchi’s lab focused on how the brain develops while Young’s lab had the expertise to transplant adult neural stem cells into the brain.

Sakaguchi, associate professor of zoology and genetics, and Young, a neurobiologist at Harvard Medical School, have received recognition for their research on the structural integration of transplanted adult neural stem cells into the eyes of mice, rats and Brazilian opossums.

Stem cells, often called the “master cells” of the body, are able to divide indefinitely when placed in cell culture and can give rise to a myriad of more specialized cell types.

When Sakaguchi and Young began their initial transplants, the question of whether adult neural stem cells could be successfully transplanted, survive and integrate into the tissue of the eye was already an active area of research. Considerable research efforts are focused on using adult-derived stem cells to replace damaged and diseased cells in our bodies.

“They found that when these adult neural stem cells were transplanted into a mature eye, the cells would survive, but [the cells] really wouldn’t do much,” Sakaguchi said.

The stem cells could survive the transplant, but not much ground could be gained if they did not integrate into the tissue. Sakaguchi considered the influence age might have on the integration, survival and function of the adult neural stem cells. His intuition proved to be valuable.

“We found some very remarkable results,” he said.

By transplanting adult neural stem cells into a young eye, the cells were able to integrate into the tissue, Sakaguchi said. In order to test their hypothesis completely, he and Young needed to perform transplants in an animal model where they could study different developmental stages.

“Looking at how the host environment might influence transplanted neural stem cells, one would want a model animal system where one could look at all phases of life,” Sakaguchi said.

They decided to turn to the Brazilian opossum. Opossums are marsupials, like kangaroos, but lack a pouch. When opossums are born, they are extremely immature developmentally, more so than a newborn mouse or rat, he said.

With opossums, scientists have a model with which they can transplant neural stem cells at various stages of development from very young to mature as well as into adult ages. Sakaguchi’s lab is attempting to explain why the young eye tissue is more receptive to integration of the transplanted cells than the mature eye tissue.

“We are trying to understand how the host environment influences neural stem cell survival, integration and differentiation,” Sakaguchi said.

The next step in their research involves acquiring the proper equipment to monitor electrical activity from the transplanted cells.

“One of the biggest issues in this area of research is trying to determine if the cells transplanted are actually functioning,” Sakaguchi said.

It takes considerable funding to carry out the research, he said.

The research that Sakaguchi is performing is paving new ground by pursuing the idea that cells derived from the brain may be able to change into retinal neurons, Young said.

“This idea has been hinted at in the past, but Don was the first one to show it,” Young said.

Sakaguchi and Young’s research has been funded by the National Institutes of Health, The Glaucoma Foundation and private donations.