Neuronal Stem Cells Are Transplanted Into Diseased Eye, Extend Into Optic Nerve

BOSTON - Neural progenitor cells transplanted to the diseased retina of rats have integrated into the eye, taken on some of the characteristics of retinal cells and extended into the optic nerve, a necessary prerequisite to re-establishing connections to the brain, researchers reported today (Sept. 27, 2000).

The research shows promise for a new type of cellular transplantation aimed at helping millions of people whose vision has been impaired by retinal damage due to illnesses such as macular degeneration, glaucoma, retinal detachment and diabetic retinopathy, as well as brain disorders in which new neurons are needed, such as stroke, Alzheimer's disease, Parkinson's disease, and other forms of central nervous system injury such as spinal paralysis.

In the first use of neural stem cells in a diseased retina - in this case using cells derived from the hippocampus of adult rats - the researchers found that the cells not only migrate to the right place and appear to take on the right characteristics, but also show early signs of trying to connect the retina to the brain - a necessary step in restoring sight.

"This is very encouraging, since there are many blinding diseases of the retina for which there are no cures," said Michael Young, Assistant Scientist at The Schepens Eye Research Institute who led the studies. "If we can transplant new cells into the retina, we may be able to restore sight in instances where visual loss is caused by damaged retinal cells."

The research was reported in the journal Molecular and Cellular Neuroscience (Academic Press, September 2000). In addition to Young, co-authors are Jasodhara Ray, Ph.D., of the Salk Institute for Biological Studies; Simon J.O. Whiteley, Ph.D., of The Schepens; Henry Klassen, M.D., Ph.D., of Children's Hospital of Orange County, Calif.; and Fred H. Gage, Ph.D., of the Salk Institute.

Another crucial finding was that the transplants worked best when the retina was sick. In healthy retinas, the stem cells did not transform into retinal cells; in fact, they did not even migrate to the retina.

"These cells somehow sense that they are needed, and begin to differentiate into cells that could take on the job of retinal neurons," Young said. "It is exciting that neural progenitor cells are capable of responding to injury cues in the mature central nervous system. We are optimistic that this technique will one day restore vision to those who have been blinded by disease or injury."

The retina is in the back of the eye, similar to the film in a camera. It is as thin and delicate as wet tissue paper, yet has the complex job of collecting the light that enters the front of the eye and converting it to electrical signals and then transmitting this information to the brain. Because they are neuronal cells, damaged retinal cells normally will not repopulate. In the center of the retina is the macula, the tissue responsible for detailed vision such as recognizing faces and reading.

Young and colleagues injected adult rat hippocampal progenitor cells into eyes of rats with retinal degeneration. The retina of 1-, 4- and10-week-old rats exhibited widespread incorporation of donor cells, while 18-week-old recipients showed acceptance but fewer cells. The cells were put into the vitreous, the gel-like substance in the middle of the eye, and migrated into the retina.

"As the rat retina is fully developed before the end of the third postnatal week, the widespread incorporation seen at 4 and 10 weeks indicates that developmental maturity is not a barrier to the acceptance of (neural stem cells) by the diseased mammalian retina," the authors write. "These results reinforce the conclusion that the neuronal repopulation presented here represents a form of morphological integration, rather than simply cellular infiltration or random migration and neurite extension."

The researchers caution that they are a long way from transplanting stem cells in humans. "We first need to show that this technique can actually restore sight in animals," Young said.

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The research was supported by the National Eye Institute, the Minda de Gunzburg Research Center for Retinal Transplantation at The Schepens Eye Research Institute, and the American Paralysis Association.

The Schepens Eye Research Institute, an affiliate of Harvard Medical School, is the largest independent eye research center in the nation, both in size of faculty and support from the National Eye Institute. The Institute, begun in 1950, has a renowned faculty of more than 60 scientists, including immunologists, molecular and cell biologists and physicists who investigate cures for blinding diseases and aids for people with low vision. Many diagnostic techniques and devices, surgical methods and medications related to eye disease were developed by Institute faculty.