Newly-discovered “youth” protein protects against aging conditions of the eye

July 21, 2022
Newly-discovered “youth” protein protects against aging conditions of the eye

An eye protein abundant in young retinas has been found to promote a cellular recycling process that maintains vision, say scientists at the US National Eye Institute (NEI). The protein in question is called pigment epithelium-derived factor (PEDF) contained in the retinal layer at the back of the eye. PEDF plays an important mediatory role in a natural recycling process in the eye.

Levels of PEDF, however, decline as we age leading to conditions such as age-related macular degeneration (AMD), and ultimately, vision loss.

The protein is produced by the retinal pigment epithelium (RPE), a layer of support cells which sits just beneath the retina’s light-sensing photoreceptor cells. The retina is composed of several layers and forms part of the eye structure that functions to detect and process light signals, which the brain uses to generate vision. 

The RPE layer is concerned with recycling and replenishing the outer edges of the retina’s photoreceptor cells through lipid metabolism – photoreceptors eventually become unable to detect light if the RPE cannot provide recycled components back to them. In people with AMD or certain types of retinal dystrophies, senescence (aging), or death of RPE cells in the retina leads to vision loss.

In order to establish whether declining PEDF levels actively drives vision loss, the scientists studied the cellular structure of mice engineered to lack the PEDF gene. The cells had enlarged RPE cell nuclei, which is believed to be indicative of changes to the cells’ DNA. The cells had also switched on four genes linked to aging, and levels of a critical PEDF receptor were far below normal.

Further, there was a significant buildup of unprocessed lipids and outer segment components in the RPE layer of the retina.

“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 NEI staff scientist Ivan Rebustin. “It seems there’s some sort of feedback-loop involving PEDF that maintains the levels of [the PEDF receptor] and lipid metabolism in the RPE.”

As the alterations in the RPE layer and changes in gene expression are similar to those seen in aging retinas, it positions PEDF as an important protective and regulatory protein in age-related changes to the photoreceptor cells of the retina, and of optimum vision.

“We always wondered if loss of PEDF was driven by aging, or was driving aging,” said Patricia Becerra, Chief of NEI’s Section of Protein Structure and Function. “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.”


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