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Sight restored in mice with glaucoma-like condition in 'milestone' research

Alexandra Thompson
·4-min read
Visually impaired man using tactile tiles to navigate city, finishing crossroad
Glaucoma, usually brought on by a build-up of pressure in the eye, is a leading cause of blindness. (Getty Images)

Vision has been restored in mice with a glaucoma-like condition, research suggests.

The common disorder, a leading cause of blindness, comes about when the optic nerve that connects the eye to the brain becomes damaged, usually due to a build-up of fluid.

Existing treatments like eye drops and surgery can prevent vision deteriorating further, but cannot reverse sight already lost.

Scientists from Harvard, however, managed to restore vision in mice with a glaucoma-like condition by delivering three “youthful” genes to the rodents’ retinas.

Read more: Flipping protein 'off switch' may reverse vision loss

This thin layer of tissue receives light from the eye’s lens, converting it into signals that are transmitted to the brain for recognition.

If the “milestone” results are replicated in further animal studies, clinical trials in human patients could begin within two years, according to the scientists.

The human eye is an organ which reacts to light and pressure. As a sense organ, the mammalian eye allows vision. Human eyes help to provide a three dimensional, moving image, normally colored in daylight. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth
Glaucoma occurs when the optic nerve, which connects the eye to the brain, becomes damaged. (Getty Images)

“Our study demonstrates it’s possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function,” said study author Professor David Sinclair.

“If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large.”

Read more: Brain injection rids rats of type 2 diabetes

Glaucoma is responsible for around one in 10 (10%) cases of registered blindness in the UK.

In the US, more than 3 million people live with glaucoma, making it the leading cause of irreversible sight loss.

Watch: Glaucoma study emphasises need for regular eye checks

The scientists first used a harmless virus to deliver three youth-restoring genes —known as Oct4, Sox2 and Klf4—to the retinas of mice with optic nerve injuries.

This approach was based on a theory as to why animals, including humans, age.

With time, cells are thought to become progressively worse at “reading” genes, causing them to malfunction.

Read more: Hopes of new pancreatic cancer drug in mouse study

During embryonic development, so-called DNA methylation is laid down to produce various cell types. This occurs when substances derived from methane are added to a DNA molecule, changing its activity but not the genetic sequence.

Over time, youthful patterns of DNA methylation are lost, resulting in genes inside cells being turned off and subsequent impaired cellular function.

Oct4, Sox2 and Klf4 are thought to return cells to an embryonic state.

After administering the genes via the virus, the number of retinal ganglion cells in the mice doubled. Ganglion cells process visual information that begins as light entering the eye and transmit it to the brain.

Results, published in the journal Nature, further revealed the mice’s optic nerve regrowth increased five-fold.

The scientists were relieved to find the treatment did not induce tumours, which has occurred in previous similar studies.

“At the beginning of this project, many of our colleagues said our approach would fail or would be too dangerous to ever be used,” said lead author Yuancheng Lu.

“Our results suggest this method is safe, and could potentially revolutionise the treatment of the eye and many other organs affected by ageing.”

In a second part of the experiment, the scientists administered the three-gene cocktail to mice with a condition mimicking glaucoma.

The results suggest the treatment increased nerve cell electrical activity and notably improved vision, as measured by the rodents’ ability to see moving vertical lines on a screen.

This occurred after the glaucoma-induced vision loss had already set in.

“Regaining visual function after the injury occurred has rarely been demonstrated by scientists,” said co-author Dr Bruce Ksander.

“This new approach, which successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.”

The treatment worked similarly well in elderly mice with diminishing vision due to normal ageing, with the therapy leading to a level of gene expression and electrical signalling similar to that of young rodents.

When analysing the treated cells, the scientists found reversed patterns of DNA methylation, suggesting this is what drives ageing.

“What this tells us is the clock doesn’t just represent time, it is time,” said Professor Sinclair.

“If you wind the hands of the clock back, time also goes backward.”

Dr Andrew Huberman, from Stanford University, said the results represent “a milestone in the field”, according to France 24.

“For decades, it was argued understanding normal neural developmental processes would one day lead to the tools to repair the aged or damaged brain.

“[This] work makes it clear: that era has now arrived.”

Watch: Exercise slows vision loss, study suggests