How Can Mice Restore Vision?

Harvard Medical School (HMS) and Mass Eye and Ear scientists made old mice see better again by making their eye nerve cells act young. They used a virus to give the mice three special genes, Oct4, Sox2, and Klf4, which usually work when animals are babies. Zhigang He, PhD, a brain and eye expert at HMS, and his colleagues, David Sinclair, PhD, and Yuancheng Lu, PhD, wanted to know if old mice could fix their eyes like young mice. They put the three genes into the eye nerve cells of adult mice with eye injuries. After treatment, more eye cells survived, and the nerves grew back five times better. Then, Bruce Ksander, PhD, and Meredith Gregory-Ksander, PhD, eye experts at HMS, did more tests. They made old mice with eye problems see better by using the same genes. This big discovery, published in Nature last month, shows it might be possible to make complex eye cells younger safely. This research could lead to new treatments to bring back lost vision.

Researchers reversed damage to the mouse eye (shown in a microscope image of a healthy animal, above) by genetically reprogramming neurons that make up the optic nerve.NIGMS/BRYAN WILLIAM JONES/ROBERT E. MARC/UNIVERSITY OF UTAH/SCIENCE SOURCE

In another experiment, the researchers tested the reprogramming-factor genes on healthy middle-aged mice, which had lower visual acuity compared to younger mice. After treatment, the older mice exhibited similar acuity scores to their younger counterparts. The scientists observed DNA methylation and gene expression patterns in these cells resembling those of younger animals. Sinclair suggests that the cells responded to the reprogramming factors by adjusting their gene expression to resemble a more youthful state, hinting at the possibility that cells retain an epigenetic memory of their past, though how this memory is stored remains unclear. Sinclair's company, Life Biosciences, is exploring treatments for age-related diseases, including glaucoma, and plans to evaluate the safety of this gene therapy approach in larger animals. Yun underscores the complexity and potential risks associated with resetting the epigenome to reverse aging or treat diseases. Reprogramming cells to an earlier state could lead to uncontrolled growth and cancer. Further studies are needed to assess how the three factors affect different cell types and tissues and confirm the long-term maintenance of a youthful state in reprogrammed cells. She notes that there is still much research ahead in this field.

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