See How They See: Immature cells boost vision in night-blind mice

Transplanted retinal cells can restore some vision in mice with degenerative eye disease, experiments show. The new findings could point the way toward treatments for several forms of progressive blindness, including macular degeneration, which affects an estimated 6 million people nationwide.

SIGHT LINE. These rod photoreceptor cells, shown in green, are at the optimal developmental stage for transplantation into blind mice. Other cells appear red. Swaroop Lab./Univ. of Michigan Kellogg Eye Center

For years, researchers have aimed to transplant stem cells to replace light-sensitive rod cells that had degenerated. Rods provide vision in near darkness and are usually the first photoreceptor cells to die in blindness.

Animal experiments, however, have shown limited success, in part because stem cells tend not to develop into rods after transplantation. Mature rod cells, by contrast, haven’t integrated well with existing tissues.

In the new study, researchers transplanted retinal cells from fetal mice, newborns, or adults to mice that, because of genetic defects, had lost their rods and thus their night vision.

Some retinal cells from the newborns became functioning rods after transplantation. By contrast, only a few of the cells from the fetal mice and none of those from the adults became functional.

To determine whether transplanted cells were working, the scientists exposed the recipient animals to light. Pupil dilation in response to low light demonstrated that the eye’s neural circuits were intact in the majority of the animals that received immature photoreceptor cells, reports retinal surgeon and study coauthor Robert E. MacLaren of Moorfields Eye Hospital in London. Electrical impulses recorded in the visual area of the brain also indicated that the transplants had restored some vision.

The developmental stage of the transplanted cells was the crucial factor, MacLaren, neurobiologist Anand Swaroop of the University of Michigan in Ann Arbor, and their colleagues conclude in the Nov. 9 Nature.

The new study may be the first to systematically compare nervous system cells transplanted at different stages of maturity, says Thomas A. Reh, a retinal-developmental biologist at the University of Washington in Seattle. Similar rigor could aid researchers seeking to transplant brain cells into people with Parkinson’s disease and other neurological problems, he says.

For vision repair, Reh adds, a surprising aspect of the new report is that cells well on the path to becoming rods—rather than stem cells with more developmental options—appear to be the most promising transplant candidates.

The maturity of the successfully transplanted mouse cells corresponds to that of human retinal cells late in the first trimester of pregnancy, Swaroop says.

Says MacLaren, “At the moment, we simply don’t have a source of the immature photoreceptor cells.”

However, scientists might someday convert stem cells from either adults or embryos into cells that would succeed as transplants. Last year, Reh and his team reported coaxing embryonic stem cells to resemble immature rod cells.

Using those ripened stem cells, the team is now attempting to replicate MacLaren’s results. The experiments could lead to trials that use embryonic stem cells in people with progressive blindness.

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