Worldwide, there are an estimated 285 million visually impaired people, of which 39 million of them are blind. Now, a team of scientists from Harvard Medical School (USA) has successfully restored vision in mice by turning back the clock of eye cells in the retina to regain youthful genetic function. This is the first demonstration that complex tissues, such as nerve cells in the eye, can be safely reprogrammed at an earlier age. In addition to this, the researchers were able to reverse vision loss in animals with a condition that mimics human glaucoma, one of the leading causes of blindness worldwide.
“Our study demonstrates that it is possible to safely re-age complex tissues such as the retina and restore their youthful biological function,” explains David Sinclair, study leader published in the journal Nature .
In their research, the team used an adeno-associated virus (AAV) as a vehicle to deliver three youth-restoring genes (Oct4, Sox2, and Klf4) into the retinas of mice that are normally activated during embryonic development . The three genes, along with a fourth, which was not used in this work, are collectively known as Yamanaka factors (after Shin’ya Yamanaka, who received the Nobel Prize in Medicine in 2012 for his studies with induced pluripotent stem cells ).
The treatment had a lot of beneficial effects on the eyes. First, it promoted nerve regeneration after optic nerve injury in mice with damaged optic nerves. Second, it reversed vision loss in animals with a condition that mimicked human glaucoma. And third, it reversed vision loss in elderly (12-month-old) animals without glaucoma. In mice with glaucoma, it increased the electrical activity of nerve cells and sharpened eyesight. In the elderly, the electrical signals from the optic nerve cells were similar to those of the young mice as well as restoring vision. There had been a reversal of DNA methylation patterns.
Although they reside in the eyes and therefore outside the skull, retinal ganglion cells (RGC) are neurons in the brain; so the same approach could work in other organs of the body.
This technique is based on the epigenetic clock, the aged equivalent of the biological clock. It tells the genes to turn on or off. Changes, whether through our DNA or the environment, are believed to cause cells to malfunction and trigger age-related diseases. One of the most important is methylation, the addition of a chemical. Over time, youthful patterns are lost ; the genes that should be turned on are turned off and vice versa, resulting in impaired cell function. What this job did is erase these “traces”.
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A cure for blindness?
It is the first time that a complex tissue has been “reprogrammed”. Clinical trials are expected in just two years, and this innovative technique is expected to work in humans and to treat other neural diseases, including dementia. But for the moment, these results are just a proof of concept that will need to be replicable in different animal models before trying any human experiments.
With additional research, this approach has the potential to promote tissue repair in various organs and pave the way for treatments that reverse human aging and age-related diseases.
“If confirmed by further research, these findings could revolutionize the treatment of age-related visual disorders, such as glaucoma, and the areas of biology and medical treatment of the disease in general,” Sinclair said.
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Note: In the current year-long study, none of the mice showed negative side effects.
Referencia:Reprogramming to recover youthful epigenetic information and restore vision, Nature (2020). DOI: 10.1038/s41586-020-2975-4 , www.nature.com/articles/s41586-020-2975-4
