Professor studies stem cells’ effect on damaged nerves

Amy Wahle

Stem cell research is being conducted in the ISU zoology and genetics department regarding human eye diseases.

Stem cells are undifferentiated, young cells with the ability both to multiply and to change into specific kinds of cells, said Donald Sakaguchi, associate professor of zoology and genetics.

His research is working to develop “effective strategies to repair the damaged human brain,” he said.

Sakaguchi said his research looks specifically at glaucoma — a human eye disease that can lead to blindness.

“The model brain structure we work with is the eye [and] the brain damage in this case is blindness,” he said.

Sakaguchi said the eye is a good model system to work with because the retina is derived from the same structure that gives rise to the brain.

Sakaguchi said he hopes the research will lead to “more general applications of regenerative medicine” for neural damage and diseases like Parkinson’s and Alzheimer’s diseases and spinal cord damage.

Sakaguchi’s laboratory uses adult rodent models of glaucoma, into whose eyes neural stem cells are transplanted to repair the brain damage.

The lab joins forces with other researchers around the country, he said. For example, Michael Young, assistant professor of ophthalmology at Harvard University, provides the transplant cells of mice and rats for Sakaguchi’s lab.

Young said this area of research is not using the ethically controversial embryonic stem cells because “we don’t know how to turn an embryonic stem cell into a retinal cell.”

Just because research is able to isolate the embryonic stem cells doesn’t mean all researchers are able to differentiate them, Young said. Embryonic stem cells have only a few specific classes of neurons that have been found, he said.

Young said the stem cells this research is using are committed to retinal type cells in order to restore the retinal degeneration, that occurs in the case of glaucoma.

How it works

Sakaguchi said there are two parts to his work with stem cells.

First, tissue cultures using the stem cells are studied to understand their biology and control the tissue environment. Then, the cell transplantation takes place to learn about stem cell survival, differentiation and integration into the new environment.

“The animal models are induced with glaucoma and then retinal stem cells are transplanted into the eye in order to restore sight,” Sakaguchi said. “It is easier to isolate animal tissue [and] there is likely to be similarities from mice or rats compared to human stem cells.”

Sakaguchi said it is essential that he collaborate with other researchers to accomplish the ultimate goal of developing these strategies to repair the brain.

Randy Kardon, who specializes in ophthalmology and visual sciences at the University of Iowa Hospital, called himself the “clinic arm” of the research group.

“I see a lot of optic nerve diseases other than glaucoma,” he said. “What we bring to the table is a method to detecting and monitoring damage or return of function to the optic nerve.”

Kardon said he has been able to modify an automated system of examining the eye for a very small lab animal. A very high magnification on a telephoto lens of an infrared sensitive video camera is used. This allows researchers to record pupil movement of very small animals’ eyes to detect the nerve damage.

“The most important surprise [is that] we have found some function happens on its own,” Kardon said. “It is important to understand [whether] the intervention is due to the stem cell or the natural regeneration.”

Sinisa Grozdanic, graduate assistant in biomedical sciences and former student of Sakaguchi, compliments the research with his background study of glaucoma.

He said the research must try to produce factors in stem cells that might lead to recovering diseased neurons in the retina. The research has found the stem cells are able to survive after they are transplanted, Grozdanic said.

“We noticed [the stem cells] started to differentiate into what looks like neurons,” he said.

Grozdanic said the recovery has not been statistically significant and he doesn’t know if the cells are functional. He said more research must be done.

The Glaucoma Foundation, National Institute of Health, Carver Trust and other private donations fund Sakaguchi’s research.