SUNY Upstate researchers look to retinal stem cells for clues to treating vision disorders

SUNY Upstate Medical University researchers are conducting a two-phase laboratory study of retinal stem (RS) cells, rare cells that hold promise in treating retinal diseases, such as retinitis pigmentosa and macular degeneration. The study, "Retinal Stem Cell Culture and Characterization," is funded through a four-year $200,000 grant from the Research to Prevent Blindness organization.

Phase one of the study, to be conducted by Michael E. Zuber, Ph.D., and Andrea S. Viczian, Ph.D., will identify the genes that produce RS cells. They will then investigate the potential for producing quantities of these stem cells in culture to better understand how they generate seven different classes of cells that perform specific functions within the retina. This understanding could be used to determine effective therapies, possibly cures, for retinal disorders.

Adult retinal stem cells isolated from donor tissue can differentiate into many of the cell types of the retina, such as photoreceptor cells. "Although promising, the use of RS cells to treat retinal injuries and degeneration is hampered by difficulties in isolating and culturing sufficient quantities of these cells," said Zuber, a research assistant professor in the Departments of Ophthalmology and Biochemistry and Molecular Biology. "More importantly, there is little information available on how to control the differentiation of RS cells into specific retinal cell types."

To begin their study, the researchers examined how embryonic retinal stem cells form and differentiate in the frog. "The eye begins as a patch of ectoderm cells that first form neural tissue, then RS cells," said Zuber. "We investigated the genes responsible for this process during the eye formation in the frog and found that at most eight eye field transcription factors are required for normal eyes to form."

Upon further investigation, the team also discovered that these same factors are expressed simultaneously in developing frog embryonic RS cells.

"Remarkably, when we forced the expression of the factors together in frog embryos, the animals developed a third eye," said Viczian, postdoctoral fellow in SUNY Upstate's Departments of Ophthalmology and Biochemistry & Molecular Biology. "These results demonstrated to us that by the simple coordinated expression of the factors we can generate RS cells capable of giving rise to all of the cells of the adult eye, providing us with a very powerful tool for identifying the set of genes necessary to convert ectoderm into retinal stem cells that can differentiate into the various retinal cell types."

The research team is now attempting to generate these same tissues in the culture dish.

"The ultimate goal of our research is to identify the genes that are required to transform pluripotent stem cells into retinal stem cells and differentiated retinal cells in the laboratory," said Viczian. Pluripotent stem cells are those cells which may still differentiate into various specialized types of tissue elements.

"The unlimited supply of retinal stem cells in the laboratory dish using a patient's own, readily available tissues would eliminate the risk of host rejection when using replacement therapies, such as cell transplantations, to treat those suffering from retinal damage or degeneration," Viczian said.