09 November 2006

Three Blind Mice: A Thing of the Past?

It's been quite a week for lab mice ...

The latest chronicling of their fortunes comes from Rick Weiss of the Washington Post, who reports on efforts to restore eyesight to the blind:

WASHINGTON -- Blind mice regained some ability to see after getting transplants of cells taken from the eyes of other mice, strengthening the prospect that it may someday be possible to restore vision in some people who have lost most or all of their eyesight, scientists reported Wednesday.

Researchers in London and Michigan who did the work warned that it would be years before similar efforts might be tried in people who have lost their vision from macular degeneration, the kind of blindness addressed in the mouse study.

But they said the new study showed for the first time that light-detecting retina cells -- which in this case were taken from other animals but which scientists have begun to grow from human embryonic stem cells -- can orient themselves properly after being injected into a blind eye, connect to other nerve cells and communicate appropriately with visual centers in the brain.

"It's still at the research stage, but it's very promising," said Anand Swaroop, a professor of ophthalmology, visual science and human genetics at the University of Michigan Medical School's W.K. Kellogg Eye Center in Ann Arbor.

Swaroop led seminal work in recent years that identified the cells in the eye's retina that grow into "rod" cells during fetal development -- the cells that are responsible for black-and-white vision. He was one of nine researchers involved in the new work, led by Robin Ali of London's Institute of Ophthalmology and described in today's issue of the journal Nature.

The new work is not the first to show evidence of restored visual acuity after the injection of immature retinal cells into failing eyes. But in previous studies, including one released in September involving rats, failing eyesight was salvaged by transplanting cells whose job is to nourish light-detecting cells. That approach might help people who are going blind because of the gradual loss of their own nourishing cells, but it would be of no use to those who have already lost vision because of the failure of their light-sensitive cells, known as rods and cones.

By contrast, the new work involved transplants of immature rod cells themselves. That means it holds the potential to restore vision even in those who have already lost those crucial cells, scientists said.

"This opens the whole possibility of restoring vision for people who have already become blind," said Robert Lanza, who is pursuing related work with embryonic stem cells at the biotech firm Advanced Cell Technology in Worcester, Mass. "It suggests you can really reconstruct the retina, something no one was sure we could biologically achieve."

The new work began with the retrieval of cells from the retinas of newborn mice, whose eyes are in an early stage of development that is equivalent to two or three months of fetal development in humans.

Using a cell-sorting technique developed in Swaroop's Michigan laboratory, the team isolated a certain kind of cell that is not a stem cell -- that is, it is no longer capable of becoming any number of different kinds of cells but is committed to becoming a rod cell -- but is not yet fully developed.

The researchers injected about 1,000 of these cells into the retinas of mice that had an inborn defect that leads to blindness in much the same way as macular degeneration, the leading cause of blindness in humans 55 and older. There the cells completed their development into light-detecting rods.

Autopsy exams showed that the cells had made connections to surrounding nerve cells that feed visual signals to the brain. In followup studies, blind mice were exposed to light a few weeks after their cell transplants. The animals' brains responded to the light and their pupils narrowed, showing that those nerve connections were appropriate and functional.

Lanza said he has been able to coax human embryonic stem cells to become cells that look very much like the immature rod cells used in the study. Mature rod cells are not malleable enough to work, Ali's team found, and totally immature stem cells present a risk of tumor growth.

While one option is to retrieve the useful cells from aborted fetuses, Lanza believes researchers will be able to grow them en masse from embryonic stem cells.

Among other important studies yet to be done, Swaroop said, are ones to determine how long the transplanted cells live and whether any of the transplanted cells could pose a risk of tumor formation.

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