Healing of blindness on the horizon after fully restored vision loss in mice with glaucoma

Doctor: “Our results suggest that this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging.

BOSTON, Mass .– A cure for blindness may be on the horizon after a team from Harvard Medical School reported successfully restoring glaucoma vision loss in mice.

Scientists achieved the feat by reversing the clocks of eye cells using a cocktail of proteins. This is the first time that complex tissue has been “reprogrammed” at an earlier age. Clinical trials are expected to begin within the next two years. This revolutionary technique is expected to work just as well in humans and may also defeat other neurological diseases, including dementia.

The researchers add that this new study sheds new light on the mechanisms of aging; pointing to a therapeutic target for a host of conditions.

“Our study demonstrates that it is possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function,” lead author Professor David Sinclair said in an article university outing.

According to the Centers for Disease Control and Prevention, more than four million people over the age of 40 are legally blind or visually impaired in the United States. The Harvard team used a harmless virus to introduce three genes into the retina of laboratory rodents with glaucoma – the most common cause of human blindness.

“The results could be transformative for vision diseases like glaucoma”

Called Oct4, Sox2 and Klf4, these proteins are transcription factors activated during embryonic development. The researchers say the procedure also worked well in elderly mice whose eyesight diminishes due to normal aging.

Subsequently, the gene expression patterns and electrical signals of the cells returned to a state similar to that of young mice, including improved vision. The study’s authors explain that their technique could actually heal damaged optic nerves in mice with glaucoma.

Although they reside in the eyes and technically outside the skull, retinal ganglion cells (RGCs) are neurons in the brain. The team believe their approach may work in restoring other organs as well.

“If confirmed by further studies, these findings could be transformative in the care of age-related vision diseases such as glaucoma and in the fields of biology and medical therapeutics for the disease in general.” , explains Professor Sinclair.

The study focuses on the “epigenetic clock”, the aging equivalent of the body clock. It tells genes to turn on or off. It is believed that changes, whether through our DNA or the environment, cause cells to malfunction and trigger age-related illnesses.

One of the most important genetic processes is methylation. DNA methylation can prevent certain genes from being expressed. This, for example, can prevent the genes responsible for tumors from turning on and causing diseases like cancer.

At the same time, genes that should be turned on are turned off and vice versa, resulting in impaired cell function. Over time, methylation also causes DNA to lose its younger patterns.

Like having new eyes

Previous work achieved the feat in cells grown in laboratory dishes, but failed to demonstrate the effect in living organisms. Professor Sinclair and his team have targeted cells in the central nervous system because they are the first place in the body affected by aging. After birth, its ability to regenerate rapidly decreases. The results show that the treatment doubled the number of surviving cells after optic nerve damage and increased regrowth five times.

“At the start of this project, many of our colleagues said that our approach would either fail or be too dangerous to ever be used,” says study author Dr. Yuancheng Lu. “Our results suggest that this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging. “

In mice with glaucoma, it stimulated the electrical activity of nerve cells and improved eyesight. They could see moving vertical lines better on a screen, even after vision loss had already occurred.

“Recovery of visual function after injury has rarely been demonstrated by scientists,” adds co-author Professor Bruce Ksander. “This new approach, which successfully reverses several causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.”

Treatment could help older people too

The treatment worked just as well in 12-month-old mice whose vision was reduced due to normal aging. These mice are the equivalent of a person in their sixties. Analysis of molecular changes in treated cells identified inverted patterns of DNA methylation, suggesting it is a determinant of aging.

“What this tells us is that the clock doesn’t just represent time, it’s time,” Sinclair concludes. “If you wind up the hands of the clock, time also goes back. “

The team describes the results so far as “encouraging”. Full-body treatment of the mice with the three-gene procedure produced no negative side effects after one year of testing.

Results appear in the journal Nature.

SWNS writer Mark Waghorn contributed to this report.