Healthy Vision Month: Age Reversal and Glaucoma Induced Vision Loss

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July marks the start of Healthy vision month, an awareness-raising initiative led by the National Eye Institute which aims to emphasize the importance of eye health and protection throughout the aging process. As the current scientific understanding of aging expands, so does knowledge of the potential underlying mechanisms that contribute to physical and cognitive degeneration.

A proposed cause of aging is the accumulation of epigenetic noise – or disturbances in gene expression patterns – which lead to decreased tissue function and reduced regenerative capacities. In a recent to study, researchers at Harvard Medical School (HMS) addressed the epigenetic-based theory of aging, which postulates that changes in the epigenome cause cellular dysfunction and age-related disease over time.

Their research continues to explore whether DNA methylation causes cellular change and whether restoration of functionality in living organisms is possible. The results report restored vision in mice achieved by restoring aged retinal cells to their youthful function and reversal of vision loss in mice with disease mimicking human glaucoma.

Epigenetic reprogramming in mice

Proof of concept to study represents the first successful attempt to reverse the biological clock in animals via epigenetic reprogramming. To prove this, the team of researchers looked at the potential to reverse the age of cells by controlling DNA methylation.

Led by Harvard Medical School researcher Yuancheng Lu, the study authors examined whether the regenerative capacity of young animals can be replicated in adult mice by delivering a modified combination of three genes via an adeno-associated virus ( AAV) in the retinal ganglion cells of adult mice with optic nerve damage. They targeted the cells of the central nervous system because it is the first part of the body affected by aging.

“Having already found evidence for epigenetic noise as an underlying cause of aging, we wondered whether mammalian cells could retain a faithful copy of early-life epigenetic information that could serve as instructions to reverse aging.” , commented the research team.

Restore eyesight and rejuvenate cells

Lu and his colleagues found that the treatment had multiple beneficial effects on the eye health of mice; it promoted nerve regeneration after optic nerve injury in mice with damaged optic nerves, doubled the number of retinal ganglion cells surviving after injury, and increased nerve regrowth by five. These results suggest that the modified gene combination approach is safe and could potentially be used to revolutionize the treatment of ocular degeneration as well as that of other organs affected by aging.

Following their promising findings, Lu and his team teamed up with colleagues at the Schepens Eye Research Institute in Massachusetts to perform two experiments: one to test whether the three-gene cocktail could restore glaucoma-related vision loss and one second to test whether this approach could reverse vision loss associated with the regular biological aging process.

The team found that the treatment resulted in an increase in the electrical activity of nerve cells as well as a noticeable increase in visual acuity, measured by the animals’ ability to see the moving vertical lines on a screen in a model. glaucoma. “To our knowledge, this is the first example of reversal of vision loss after glaucomatous injury has occurred; previous attempts have focused on neuroprotection delivered at an early stage to prevent disease progression, ”the authors wrote.

Likewise, the treatment had beneficial effects on the vision of elderly mice; it was able to restore vision in older mice whose vision was reduced due to normal aging. After treatment, researchers found reverse DNA methylation patterns that suggest DNA methylation is an active agent in the aging process.

“These data indicate that mammalian tissues retain a record of juvenile epigenetic information – encoded in part by DNA methylation – that can be accessed to improve tissue function and promote regeneration in vivo,” the authors concluded. .

Clinical implications

As the first results proving reversal of glaucoma-induced vision loss without associated negative side effects in the cohort, the latest results will need to be confirmed by further animal work before human trials can be initiated. Nonetheless, the success of the new approach represents a potential breakthrough in regenerative medicine and a range of possible treatment pathways for age-related health problems.

“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,” said David Sinclair, Ph.D., co-director of Paul F. Glenn Center for Biology of Aging Research at HMS, who is the lead author of the article published in Nature. “If confirmed by further studies, these findings could be transformative for the management of age-related eye diseases such as glaucoma and for the fields of biology and medical therapeutics for the disease. general, ”he explained.

Take away food

If the latest findings can be replicated and validated in future clinical trials, the three-gene combination method could enable the development of therapies that promote tissue repair across a spectrum of organs and reverse aging and related diseases. age in humans.


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