A team of researchers at Harvard Medical School (HMS) and Mass Eye and Ear have successfully restored vision in elderly mice by turning back the clock on their aged nerve cells in the retina to recapture their youthful function. The team used an adeno-associated virus as a vehicle to deliver into the retinas of mice three youth-restoring genes—Oct4, Sox2 and Klf4—that are normally switched on during embryonic development.
Zhigang He, PhD, Professor of Neurology and Ophthalmology at HMS, worked with HMS scientists David Sinclair, PhD, and Yuancheng Lu, PhD, to test whether the regenerative capacity of young animals could be imparted to adult mice, delivering a modified three-gene combination via an AAV into retinal ganglion cells of adult mice with optic nerve injury. The treatment resulted in a two-fold increase in the number of surviving retinal ganglion cells after the injury and a five-fold increase in nerve regrowth.
Following the encouraging findings, faculty members Bruce Ksander, PhD, Associate Professor of Ophthalmology at HMS, and Meredith Gregory-Ksander, PhD, Assistant Professor of Ophthalmology at HMS, then led the additional vision experiments that demonstrated further proof-of-concept with the reversal of both age-related and glaucoma vision loss in a mice model.
The team’s work, published last month in Nature, represents the first demonstration that it may be possible to safely reprogram complex tissues, such as the nerve cells of the eye, to an earlier age. This promising research may ultimately lead to a new class of therapeutics that could restore vision that has already been lost.