‘Youth’ protein may be essential for prevention and treatment

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Aging and age-related diseases affect eye health in different ways. Chris Zielecki/Getty Images
  • The ‘youth’ protein, pigment epithelium-derived factor (PEDF), protects cells in the eye’s retina from oxidative stress, according to a new animal study.
  • Researchers from the National Eye Institute (NEI) have found that declining PEDF levels may contribute to aging-related diseases of the retina.
  • Experts hope these findings will lead to the development of new therapies that can reverse or counter the effects of PEDF loss.

The retina is made up of tissues at the back of the eye that process light signals and send them to the brain. The cells of the retinal pigment epithelium (RPE) are part of this structure important for vision.

A recent animal study conducted by the national eye institutepart of the National Institutes of Healthsuggests that the loss of a certain protein could prevent RPE cells from feeding and recycling photoreceptor cells.

The result senescence or the deterioration of RPE cells can trigger the onset of diseases such as age-related macular degeneration (AMD) and retinal dystrophies. These conditions are known to cause progressive vision loss.

A team led by Dr. Patricia Becerra, Principal Investigator in the NEI’s Protein Structure and Function Section, found that pigment epithelium-derived factor (PEDF) plays an anti-aging function for RPE cells. Their findings could offer the possibility of finding new ways to treat or prevent retinal diseases associated with aging.

This study was published in the International Journal of Molecular Sciences.

The RPE produces and secretes PEDF via the Serpinf1embarrassed. PEDF is called the “youth” protein because of its abundance in young retinas.

RPE production and PEDF secretion decline during senescence and aging in eyes, skin, lungs, and other tissues.

Previous research suggests that PEDF can protect photoreceptor cells from damage and inhibit the growth of abnormal blood vessels in the eye.

However, Dr Becerra said: “We have always wondered if the loss of PEDF was due to aging or aging.”

To find the answer, Dr. Becerra and his colleagues used a bioengineered mouse model without the PEDF gene. Serpinf1.

By examining the cellular structure of the models’ retinas, the researchers found remarkable differences from the control samples from wild-type mice.

The nuclei of the RPE cells were enlarged, which could indicate differences in how the cells’ DNA was arranged. These cells had also activated four genes associated with cellular senescence and aging.

Dr. Ivan Rebustini, scientist in Dr. Becerra’s lab and lead author of the study, remarked: “One of the most striking things was this reduction in the PEDF receptor on the surface of RPE cells in mice lacking the PEDF protein. It seems there is some sort of feedback loop involving PEDF […]”

These changes led the team to conclude that declining PEDF causes retinal cells to age.

This study may uncover ways to help reduce age-related vision problems, but it has some limitations.

What causes PEDF loss?

Although research suggests that PEDF may cause aging, its results do not address the cause of PEDF loss.

In an interview with Medical News Today, Dr. Becerra explained: “In addition to PEDF, there are other proteins that are dysregulated in various epithelial tissues, including the RPE, during aging. In addition to changes in age-related protein expression and production, telomere shortening has been associated with aging and is observed in high turnover epithelial tissues, such as skin.

“Telomeres are a structure at the end of a chromosome that maintains the integrity of our genes and are a critical factor for age-related diseases. Their shortening can affect gene expression during aging; the PEDF gene, Serpinf1, is one of them,” she continued.

“However, the extent to which this leads to the loss of PEDF in the eye is unknown,” she added.

DTM also discussed this study with Dr. Howard R. Krauss, a surgical neuro-ophthalmologist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, who was not involved in this research.

Dr. Krauss shared that while “we understand the vital importance of this protein and […] that its availability decreases with age and/or degenerative disease, [w]We don’t know what is causing the loss.

He agreed that PEDF depletion is just one of many factors that cause RPEs to age. He noted that identifying more factors may be needed to reduce or reverse age-related damage.

Mouse-Human Trial Challenges

The current work analyzed mouse models, which would be difficult to translate into human trials, Dr. Krauss warned.

For example, Dr. Becerra noted that “the absence of a macula in the mouse retina means that the parallels with conditions such as age-related macular degeneration are not as clear as they might be. in a species having this structure”.

According to Dr. Krauss: “[T]here, there will be no guarantee that what may work in this mouse model will ultimately have value in humans.

Additionally, Dr. Becerra said DTM that because samples from patients without PEDF are scarce, replicating the study in humans would be difficult.

Study applications

Still, Dr. Krauss was somewhat optimistic about the implications of this NIH research.

He hopes that demonstrating the effects of PEDF loss “will now allow the use of this model to apply potential therapeutic measures to increase PEDF and/or the application of proposed therapeutic measures to counteract the adverse effects of exhaustion. of the PEDF”.

Dr. Becerra said she and her fellow researchers will continue to explore “ways to use PEDF-derived peptides or mimics as therapeutics for humans.”

Luz W. German