Scientists studying the aging process in the eye have made an important discovery around the role of a so-called "youth" protein, and shown how it promotes a cellular recycling process that maintains our vision. Experiments on mice missing this protein led to fast-tracked degeneration in the retina, indicating that the protein plays an important protective role against age-related vision loss.
Led by scientists at the US National Eye Institute, the study centers on a protein called pigment epithelium-derived factor (PEDF). This protein plays an important mediatory role in a natural recycling process in the eye. It is produced by a layer of support cells, called the retinal pigment epithelium (RPE), which sits beneath the retina's light-sensing photoreceptor cells and helps recycle and replenish them as their outer edges wear out. This ability declines as we grow older and in people with age-related macular degeneration (AMD), leading to vision loss.
"People have called PEDF the ‘youth’ protein, because it is abundant in young retinas, but it declines during aging," said Patricia Becerra, senior author of the study. "This study showed for the first time that just removing PEDF leads to a host of gene changes that mimic aging in the retina."
As PEDF is secreted by the RPE cells, it binds to a receptor called PEDF-R and helps to break down lipid molecules that enclose outer segments of the photoreceptor cells. This is a critical function of the recycling process that keeps the receptor cells fresh and functional, and while previous work has established that PEDF levels decline as we age, it has remained unclear whether this actively drives vision loss, or simply correlates with it.
So the scientists engineered mice to be lacking the PEDF gene, and studied the cellular structure of the retina. This showed that the RPE cell nuclei were enlarged, which the team believes is indicative of changes to the cells' DNA. The cells had also switched on four genes linked to aging, and levels of the PEDF receptor were far below normal. Further, the RPE layer of the retina featured a build up of unprocessed lipids and outer segment components.
"One of the most striking things was this reduction in the PEDF receptor on the surface of the RPE cells in the mouse lacking the PEDF protein," said the study’s lead author, Ivan Rebustin. "It seems there’s some sort of feedback-loop involving PEDF that maintains the levels of PEDF-R and lipid metabolism in the RPE."
These alterations in the RPE layer and changes in gene expression are similar to those seen in aging retinas. The scientists say the results therefore position PEDF as an important protective and regulatory protein in age-related changes to the photoreceptor cells of the retina, and by extension, our vision.
"We always wondered if loss of PEDF was driven by aging, or was driving aging," said Becerra. "This study, especially with the clear link to altered lipid metabolism and gene expression, indicates the loss of PEDF is a driver of aging-related changes in the retina."
The research was published in the International Journal of Molecular Sciences.
Source: National Eye Institute