Aging in the Eye Could Be Linked to a Loss of Protective Protein

Aging in the Eye Could Be Linked to a Loss of Protective Protein ...

Researchers from the National Eye Institute (NEI) claim that the loss of the protein pigment epithelium-derived factor (PEDF) may be responsible for age-related changes in the retina. PEDF protects human retinal pigment epithelial (RPE) cells against oxidative stress. Their new findings in mice may pave the way for novel therapies to treat age-related macular degeneration (AMD).

In a paper titled, PEDF deletion induces sensitivity and defects in Phagocytosis in the RPE, Patricia Becerra, PhD, is the lead author of the study.

The researchers claim that the Serpinf1 gene helps to produce PEDF, a retinoprotective protein that is downregulated by cell senescence, aging, and retinal degenerations. We examined the expression of senescence-associated genes in 3-month-old mice that had not received the Serpinf1 gene, and found that H2ax for histone H2AX protein, Cdkn1 for p21 protein, and Glb1 gene for -galact

PEDF is often referred to as the young protein because it is abundant in young retinas, but it declines as age, according to Becerra. This research demonstrated for the first time that simply removing PEDF results in a host of gene changes that mimic aging in the retina.

Researchers studied the retinal function of PEDF in a mouse model that lacks the PEDF gene (Serpin1). The researchers found that the RPE cell nuclei were larger, suggesting that changes in the cells DNA are packed.

The RPE cells had also turned on four genes associated with aging and cell senescence, and the PEDF receptor levels were significantly below normal.

According to the research's lead author, Ivan Rebustini, PhD, there is a decrease in the PEDF receptor on the surface of the RPE cells in the mouse lacking the PEDF protein. There is a feedback loop involving PEDF that maintains the levels of PEDF-R and lipid metabolism in the RPE.

According to Becerra, we always wondered if the loss of PEDF was related to aging, or was causing aging. This investigation, particularly with the clear connection to altered lipid metabolism and gene expression, suggests that the loss of PEDF is a contributor to aging-related changes in the retina.

The researchers conclude that PEDF loss is a contributor to senescence-like changes in the RPE, as well as a regulatory protein of aging-like changes related to defective degradation of the photoreceptor outer segment in the RPE.

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