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Scientists said Wednesday they have restored sight in mice through a “landmark” treatment that returns cells to a younger state and may one day help treat glaucoma and other age-related diseases.
The process offers the tantalizing possibility of effectively turning time back at the cellular level, helping cells regain the ability to heal damage caused by injury, disease, and age.
“I am excited to be able to rejuvenate organs and tissues that fail due to aging and disease, especially where there are no effective treatments, such as dementia,” lead study author David Sinclair told Agence France-Presse (AFP).
“We hope to treat glaucoma in human patients (in the trial stage) in two years,” added Sinclair, a professor of genetics at Harvard Medical School.
Treatment is based on the properties that cells have when the body is developing as an embryo. At that time, cells can repair and regenerate on their own, but that capacity rapidly declines with age. The scientists reasoned that if cells could be induced to revert to that youthful state, they could repair the damage.
To turn time back, they modified a process generally used to create the “blank slate” cells known as induced pluripotent stem cells. Those cells are created by injecting a cocktail of four proteins that help reprogram a cell.
The team did not want to reprogram the cells to the blank slate state, but rather restore them to a more youthful condition. So they tweaked the cocktail, using just three of the “youth-restoring” proteins, called OSK, in the hope that they could turn the clock back to the right point.
They targeted ganglion cells in the retina in the eye, which are linked to the brain through connections called axons. These axons make up the optic nerve, and damage from injury, aging, or disease causes poor vision and blindness.
To test the effects of the cocktail, they first injected OSK into the eyes of mice with optic nerve damage. They saw a two-fold increase in the number of surviving retinal ganglion cells and a five-fold increase in nerve regrowth.
“The treatment allowed the nerves to grow back into the brain. Normally, they would just die,” Sinclair said.
‘Big emotion’
With signs that OSK could reverse the damage caused by injury, the team set about countering the effects of the disease, specifically glaucoma, which is the leading cause of blindness in humans.
They replicated disease conditions, where a build-up of pressure in the eye damages the optic nerve, in several dozen mice. Those who received the OSK treatment saw “significant” benefits, according to the study published in the journal Nature.
The tests showed that “half of the visual acuity lost due to increased intraocular pressure was restored.” The treatment offered similarly promising results in elderly mice with poor vision caused by age.
After injecting the cocktail, the mice’s vision improved and their optic nerve cells showed electrical signals and other characteristics similar to those of the younger mice. The study was conducted over the course of a year, and the mice showed no side effects.
Andrew Huberman, a neuroscientist at Stanford University School of Medicine who was not involved in the research, said the findings “were destined to elicit great emotion.”
The results will need to be confirmed in further animal tests, with a potentially long road before humans can be treated, but Huberman said they nonetheless represent “a milestone in the field.”
“The effects of OSK in people have yet to be tested, but existing results suggest that OSK is likely to reprogram brain neurons in all species,” he wrote in a review commissioned by Nature.
“For decades, it was argued that understanding normal neural development processes would one day lead to tools to repair the aging or damaged brain … (this) work makes it clear: that era has already arrived.”
