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From the Labs: Biotechnology

New publications, experiments and breakthroughs in biotechnology–and what they mean.
June 23, 2008

Blind Mice See the Light
Researchers ­engineer sight into a broken visual circuit

Specific cells (shown here in green) in the retinas of blind mice were engineered to express a light-sensitive protein, giving the mice a rudimentary form of vision.

Source: “Light-Activated Channels Targeted to O.N. Bipolar Cells Restore Visual Function in Retinal ­Degeneration”
Botond Roska et al.
Nature Neuroscience
11: 667-675

Results: Blind mice that had been genetically engineered to produce a light-sensitive protein in their retinas developed a rudimentary sense of vision. The mice responded to moving patterns, displaying an ability to resolve fine visual details about half as well as normal mice.

Why it matters: People with macular degeneration or retinitis pigmentosa, two leading causes of blindness in the United States, lose vision when photoreceptor cells degenerate. The new results raise the possibili­ty of a thera­py that would enable their eyes to detect and respond to light even in the absence of photoreceptors, partially restoring sight.

Methods: Researchers inserted a gene for a light-sensitive protein found in algae into the retinas of mice that lacked photoreceptors. Embedded in the membranes of retinal cells that normally relay signals from photoreceptors to the brain, the protein acts as a channel that opens when hit with light. That allows positively charged ions to flood into the cells, triggering a signal that ultimately reaches the brain.

Next steps: The cells engineered to produce the light-­sensitive protein normally turn on in response to light. The researchers would like to apply their approach to cells that shut off in the presence of light, adding another layer of complexity to the restored visual system. But they must first find a way to deliver a second light-­sensitive protein specifically to those cells.

Cells Show Promise for Parkinson’s
Brain cells ­developed from skin cells help alleviate ­symptoms in rats

Source: “Neurons Derived from Reprogrammed ­Fibroblasts Functionally Integrate into the Fetal Brain and Improve Symptoms of Rats with Parkinson’s Disease”
Rudolf Jaenisch et al.
Proceedings of the National Academy of Sciences
105: 5856-5861; published online April 7, 2008

Results: Skin cells reprogrammed to act as stem cells differentiated in culture into neural stem cells. Transplanted into the brains of rodents, they were integrated into the existing brain circuitry and became functioning neurons. The reprogrammed cells, which are known as induced pluri­potent stem cells, also improved symptoms in rats modeling Parkinson’s disease.

Why it matters: Animal and human studies suggest that replacing the dopamine-­producing neurons damaged in Parkinson’s can treat the disease. But finding a source of such cells in humans has been problematic. Embryonic stem cells, which can give rise to neurons, are one potential source. But taking cells from human embryos is controversial, and embryonic stem cells are difficult to obtain. Working with reprogrammed cells might prove easier than working with embryonic stem cells.

Methods: In a dish, researchers transformed mouse skin cells into undifferentiated cells by inducing them to express four genes; previous studies had shown that those genes were able to reset the cell to its embryonic state. Then they used a previously identified set of chemicals to prompt those cells to differentiate into neurons. The cells were labeled with a fluorescent marker and transplanted into the brains of fetal mice, where they appeared to integrate into the brain as the mice grew to adulthood.

Researchers also transplanted reprogrammed cells into the brains of rats given a chemical toxin to knock out their dopamine-producing cells. The transplants repaired a motor dysfunction evident in these animals.

Next steps: The scientists are now trying to repeat the experiments with human cells. Once they develop human dopamine neurons, they will transplant them into rodents to see if they behave like the reprogrammed mouse cells. The researchers also aim to determine whether neurons derived from induced pluripotent stem cells are as stable as those derived from embryonic stem cells

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