What: An interdisciplinary team of Harvard scientists has successfully reprogrammed cells in mice to reverse vision loss from glaucoma, as well as normal (not disease-related) vision loss associated with aging in mouse models. This pioneering work 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.
Where: Yuancheng Lu et al, Reprogramming To Recover Youthful Epigenetic Information and Restore Vision, Nature, 2020.
BrightFocus Connection: Key researchers in this effort attributed their success in part to funding they received from the foundation’s National Glaucoma Research program.
Why It Is Important: As one of the world’s major blinding diseases, glaucoma destroys light-sensing retinal ganglion cells (RGCs), nerve cells that are located in the eye’s retina and connect to the vision center of the brain, together making up the visual pathway. In common with most cells of the central nervous system, adult RGCs have almost no capacity to regenerate on their own.
Now, in early proof-of-concept experiments using mice models, scientists have had success with a revolutionary new approach to treating glaucoma, as well as normal, non-disease related vision loss associated with aging, both appearing to reverse the clock. Four major research labs were responsible which, in addition to those of Drs. Ksander and Gregory-Ksander, included the labs of Zhigang He, PhD, also in Harvard’s Department of Ophthalmology, and of David Sinclair, PhD, the lead investigator on the project, who is professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School.
They used gene therapy to epigenetically reprogram the eye tissue to restore youthful gene function. This consists of reversing chemical modifications to key genes through a natural biological process of DNA methylation, when methyl groups are added to the DNA molecule. This is the key way in which gene activity is modified during life (ie, epigenetically). Following early human development, once organs are fully formed, methylation works to suppress gene transcription. Later, as we age, “accidental” alterations in the methylation pattern are believed to contribute to many diseases associated with aging.
From a set of four genes (“Yamanaka transcription factors”) responsible for reprogramming cells into their younger counterparts, the team edited only three back into mouse models. These transcription genes were discovered by Shinya Yamanaka, MD, PhD, of Kyoto University, Japan, who was awarded a Nobel Prize for the discovery in 2012. In these recent experiments, the Harvard team purposely omitted the fourth factor because it is known to induce tumor growth and reduce longevity, common risks associated with gene editing.
The treatment turned out to have multiple beneficial effects on the eye. In the glaucoma mice models, it promoted nerve regeneration and reversed vision loss following optic nerve injury. In normal mice, it reversed age-related vision loss.
These early experiments would need to be replicated in further studies, including in different animal models, before initiation of clinical trials. Given that there are no treatments available to restore vision in glaucoma patients fully, this study indicates that this might be possible in the near future. If successful, the results could be transformative, potentially paving the way for new therapies promoting tissue repair across various organs and providing a way to reverse aging and age-related diseases in humans.
- Meredith Gregory-Ksander 2019-22 NGR grant profile
- András Komáromy 2017-20 NGR grant profile (with Bruce Ksander as co-investigator)
- Meredith Gregory-Ksander 2016-18 NGR grant profile
- Meredith Gregory 2006-08 NGR grant profile
- Vision Revision: Scientists Reverse Age-Related Vision Loss, Glaucoma Damage in Mice (Harvard news release, 2020)
- Harvard Medical School Scientists Reverse Age-Related Vision Loss, Eye Damage from Glaucoma in Mice (Mass Eye & Ear news release, 2020)
- Rewinding the Biological Clock: How to Reverse Aging (Nature video, 2020)
This content was last updated on: April 1, 2021