Implanting immature retinal cells into the eyes of blind mice and making mice see again is an astonishing achievement. This breakthrough collaborative research was done by investigators at the London Institute of Ophthalmology and the University of Michigan Kellogg Eye Center.
From University of Michigan statement:
The team of scientists found that transplanted photoreceptor precursor cells survived and became integrated into the mouse retina–and that the technique succeeded because the cells were isolated when they had reached a certain level of maturity.
Rather than injecting undifferentiated and uncommitted stem cells into the retina in hopes they would develop into photoreceptors, researchers introduced cells at a somewhat later stage. These cells are referred to as “precursors”: they are immature cells that are “programmed” to be, but have not yet become, functionally mature photoreceptors–the light-sensitive cells in the retina that are essential for sight.
The findings, reported in the November 9 advance online issue of Nature, come from the collaborative research of Anand Swaroop, Ph.D., the Harold F. Falls Collegiate Professor of Ophthalmology and Visual Sciences at the University of Michigan Medical School, and Robin R. Ali, Ph.D., Professor, Division of Molecular Therapy at the Institute of Ophthalmology in London…
The technology represents a breakthrough in transplantation-based therapies for neuro-degenerative diseases. It suggests that scientists may need to introduce changes in stem cells in order for them to become highly specialized neurons.
Although the experiment has implications for human eye diseases that dim the sight of millions of people, Swaroop anticipates that several years of research using animal models and cell culture systems will still be needed before transplantation can be considered ready for testing in humans…
Drs. Ali, Swaroop and their colleagues report that the transplanted cells in diseased mouse retinas have met several essential requirements: the cells survive; correctly develop into rod photoreceptors; integrate and connect in sufficient numbers to neurons that ultimately carry visual signals to the brain; and they have proven to be functional.
The photoreceptor precursors were transplanted into three different types of mice with retinal degeneration caused by distinct genetic defects involving malfunctioning or degenerating rods. The transplanted cells survived and were functional for the duration of the study. Scientists observed improvements including pupil response to light and response to light stimuli from ganglion cells, which form the circuitry to the brain.
Swaroop explains that photoreceptors constitute “the first line of information capture in vision.” They are part of a complex sensory system that delivers visual signals to the brain. Photoreceptors consist of rods and cones, highly specialized cells that capture light and convert it into chemical signals that travel through the inner retina and optic nerve and on to the brain where signals are converted to the images we see. In the majority of macular and retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa, it is the loss of photoreceptors that leads to blindness…
The new paper shows that successful transplantation requires that cells reach a certain level of maturity before being transplanted into the eye. When the cells were transplanted at a very early stage, before they were assigned their specialized function, they survived but failed to integrate into the mature retina. Only one group of cells remained viable: cells that were not yet mature, but had developed to the point at which they were committed to becoming rods.
After almost two decades of directing fundamental research on retinal development and degenerative diseases, Swaroop believes that scientists are at last entering a period of rapid discovery.
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