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Neuronal stem cells are transplanted into diseased eye,
extend into optic nerve

Research paves way for retinal transplants to restore vision

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.

http://www.eurekalert.org/releases/seri-nsc092000.html

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