Online ISSN: 1945-4589

Aging-US: Suppressing endoplasmic reticulum stress-related autophagy

09-08-2021

Aging-US published a Special Collection on Eye Disease which included "Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury" which reported that in this study, oxidative stress, endoplasmic reticulum stress and autophagy caused by light exposure were evaluated in vitro and in vivo.

Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells.

Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.

Dr. Guang-Yu Li from The Second Hospital of Jilin University said, "Age-related macular degeneration (AMD) is a degenerative retinal disease, which often occurs in the elderly and causes irreversible loss of central vision."

"Age-related macular degeneration (AMD) is a degenerative retinal disease, which often occurs in the elderly and causes irreversible loss of central vision."

Indeed, excessive and prolonged light exposure may damage the retina and is an environmental factor that can accelerate AMD. With the rapid development of technology, many electronic devices with screens, and ophthalmic equipment with intensive illumination, have become widely used. Therefore, an increasing amount of attention has been focused on issues of light pollution and retinal light damage. Previous studies have shown that excessive intracellular ROS may lead to depletion of the GSH pool and compromise the function of PDI, which disrupts the folding process of proteins in the ER and produces a massive amount of misfolded proteins.

However, the excessive accumulation of misfolded proteins in the ER may trigger an unfolded-protein response, which may enhance protein folding ability, as well as the homeostasis of protein translation and accelerate protein degradation to recover ER function. However, prolonged autophagy may lead to cell death and is specifically termed autophagy-dependent cell death. The role of autophagy in retinal light injury is controversial.

Figure 10. Suppressing ER stress inhibits prolonged autophagy and protects the retina against light injury. The mice were intraperitoneally injected with a dose of 1 mg/kg once a day for 7 days. On the third day of administration, the mice were exposed to continuous 7000 Lux visible light for 12 h. After light exposure, the mice were fed in the animal room with the normal light/dark cycle. On the fifth day of light exposure, the mice were sacrificed, and the eyeballs were enucleated. (A) The retinas were collected, and target proteins were determined with western blotting. β-actin was referenced as an internal control. Three independent experiments are conducted three weeks apart. The results are presented as the mean± SEM. n (per group) =3, NS: no significance, *P < 0.05, **P < 0.01. (B) The retinas were sectioned and stained with H&E and photographed under a microscope. Scale bar=100 μm; 20 μm. The thickness of the outer nuclear layer (ONL) was measured and quantitatively analyzed. The results are presented as the mean± SEM, n (per group) =6, NS: no significance, **P < 0.01.

Autophagy might be a double-edged sword among the molecular mechanisms that lead to retinal light damage. Midorikawa et al. reported that moderate autophagy combined with endosomal degradation pathway activity is neuroprotective and attenuates light-dependent retinal degeneration.

The Li Research Team concluded in their Aging-US Research Output "the current study demonstrated that ER stress and autophagy are both involved in light-induced death of photoreceptors and RPE cells. As an upstream step, photo-oxidation may cause an imbalance in the cellular redox status and interrupt the folding process of proteins, further triggering ER stress in photoreceptors and RPEs. Suppressing ER stress via PERK signals may inhibit prolonged autophagy and protect photoreceptors/RPEs against light damage. Inhibiting ER stress-related autophagy is neuroprotective for retinal against light injury, which may be a potential treatment strategy for AMD."

Full Text - https://www.aging-us.com/article/103846/text

Correspondence to: Guang-Yu Li email: l_gy@jlu.edu.cn

Keywords: oxidative stress, ER stress, autophagy, AMD, PERK

About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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