Retinal aging may cause many ophthalmic diseases. In a new study, the National Eye Institute (NEI) used a mouse model to determine the role of pigment epithelium-derived factor (PEDF) in retinal aging. This finding may lead to the emergence of related treatment measures in the future.
The importance of pigment epithelium and PEDF recycling
The retina is composed of multiple layers of cells that work together to detect and process the received light signal. The photoreceptors of the photoreceptors are located in the retinal pigment epithelium (RPE), and after receiving light, the photoreceptor outer segment (POS) ) tip will wear out and fall off, and the RPE must recycle the cell debris and supply the ingredients again, otherwise these photoreceptors will lose their ability to make new segments, resulting in the eventual inability to perceive light, and the RPE must also provide nutrients, otherwise the photoreceptors may also die.
In addition to closely interacting with photoreceptors, RPE also secretes a large number of factors and signaling molecules to communicate with surrounding tissues, and PEDF is one of them. Because PEDF is abundant in young retinas, but will gradually decrease in the process of aging, PEDF was also jokingly called a “youth” protein in the past, but in fact, is the reduction of PEDF causing retinal aging, or aging has an impact on the retina , researchers have been unable to determine.
It is well established that aging or dysfunction of the RPE is responsible for vision loss in cases of age-related macular degeneration (AMD) and some retinal dystrophies. Previous studies have shown that PEDF can protect retinal cells against cell damage and abnormal growth of retinal blood vessels, and the researchers were more curious whether PEDF could also help prevent aging in RPE.
PEDF is a driver of retinal ageing-related changes
In order to confirm the actual effect of PEDF on the retina, the research team found that the lack of sprinkle1 Retinal cell structure was examined in a mouse model of a gene that causes defects in PEDF production. It was found that in addition to the enlarged nuclei of RPE cells, indicating a likely change in the way DNA stacks,sprinkle1 The deletion also increased expression of four genes associated with aging in the RPE, while levels of the PEDF receptor were also significantly lower than normal.
Binding of PEDF to its receptor PEDF-R stimulates the breakdown of lipid molecules, which is also a key process part of POS recovery. In the absence of both, the result is the accumulation of raw lipid molecules and other POS components in the RPE, similar to Gene expression changes and RPE metabolic defects were also found in aging retinas. It can be said that this study is the first to show that just removing PEDF can cause a series of genetic changes like retinal aging.
It is worth mentioning that although both PEDF and its receptor are mainly produced by RPE cells, the latter is produced by RPE cells. Pnpla2 gene expression, but with Serpinf1 Deficiencies of both were also reduced, which suggests that there appears to be a PEDF-related feedback loop that maintains levels of PEDF-R and lipid metabolism in the RPE, according to study author Dr. Ivan Rebustini.
While PEDF-negative mouse retinas appear normal at first glance, these new findings show that PEDF has an important protective role in protecting the retina from trauma and age-related wear and tear. “We’ve always been curious about whether PEDF loss is driven by or is driving aging, and the findings, particularly in part with clear links to altered lipid metabolism and gene expression, reveal that PEDF loss is a driver of retinal ageing-related changes. factor.”
References:
1.International Journal of Molecular Sciences, 2022, https://doi.org/10.3390/ijms23147745
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