Harvard scientists reverse age-related vision loss, eye damage

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In a new study, researchers have successfully restored vision by turning back the clock on aged eye cells in the retina to recapture youthful gene function.

The 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.

In addition to resetting the cells’ aging clock, the researchers successfully reversed vision loss with a condition mimicking human glaucoma, a leading cause of blindness around the world.

The achievement represents the first successful attempt to reverse glaucoma-induced vision loss, rather than merely stem its progression.

The results offer a proof of concept and a pathway to designing treatments for a range of age-related human diseases.

The research was conducted by Harvard Medical School scientists.

According to the team, the treatment had multiple beneficial effects on the eye.

First, it promoted nerve regeneration following optic-nerve injury in mice with damaged optic nerves.

Second, it reversed vision loss in animals with a condition mimicking human glaucoma. And third, it reversed vision loss in aging animals without glaucoma.

The team’s approach is based on a new theory about why we age.

Most cells in the body contain the same DNA molecules but have widely diverse functions.

To achieve this degree of specialization, these cells must read only genes specific to their type.

This regulatory function is the purview of the epigenome, a system of turning genes on and off in specific patterns.

This theory postulates that changes to the epigenome over time cause cells to read the wrong genes and malfunction—giving rise to diseases of aging.

One of the most important changes to the epigenome is DNA methylation, a process by which methyl groups are tacked onto DNA.

In the current study, the researchers hypothesized that if DNA methylation does, indeed, control aging, then erasing some of its footprints might reverse the age of cells inside living organisms and restore them to their earlier, more youthful state.

Past work had achieved this feat in cells grown in laboratory dishes but fell short of demonstrating the effect in living organisms.

The new findings demonstrate that the approach could be used in animals as well.

The team developed a gene therapy that could safely reverse the age of cells in a living animal.

They targeted cells in the central nervous system because it is the first part of the body affected by aging. After birth, the ability of the central nervous system to regenerate declines rapidly.

To test whether the regenerative capacity of young animals could be imparted to adult mice, the researchers delivered the modified three-gene combination into retinal cells of adult mice with optic nerve injury.

The treatment resulted in a two-fold increase in the number of surviving retinal ganglion cells after the injury and a five-fold increase in nerve regrowth.

The results suggest this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging.

Following the encouraging findings in mice with optic nerve injuries, the team tested the method in a mouse model of glaucoma.

The treatment led to increased nerve cell electrical activity and a notable increase in visual acuity, as measured by the animals’ ability to see moving vertical lines on a screen.

Remarkably, it did so after the glaucoma-induced vision loss had already occurred.

The team says this new approach successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant. It represents a new treatment modality in regenerative medicine.

If the findings are confirmed in further animal work, they could initiate clinical trials within two years to test the efficacy of the approach in people with glaucoma.

One author of the study is David Sinclair, a professor of genetics in the Blavatnik Institute at Harvard Medical School.

The study is published in Nature.

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