Positive Health Online

Abstract

ZHANG and COLLEAGUES, 1 Central Laboratory, Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang Province, China; 2 Central Laboratory, Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang Province, China. Electronic address: liyijie12580@126.com studied the effects of all-trans-retinal (atRAL) upon oxidative stress, autophagy and retinal pigment epithelial (RPE) degeneration.

Background

Failure of all-trans-retinal (atRAL) clearance contributes to retina degeneration. However, whether autophagy can be activated by excess atRAL accumulation in retinal pigment epithelial (RPE) cells is not known.

Methodology

This study showed that atRAL provoked mitochondria-associated reactive oxygen species (ROS) production, activated the nuclear factor (erythroid-derived 2)-like 2 and apoptosis in a human RPE cell line, ARPE-19 cells.

Results

Moreover, we found that autophagic flux was functionally activated after atRAL treatment. The antioxidant N-acetylcysteine attenuated the expression of autophagy markers, suggesting that ROS triggered atRAL-activated autophagy. In addition, autophagic cell death was observed in atRAL-treated RPE cells, while inhibition of autophagy with 3-methyladenine or LC3, Beclin1, p62 silencing ameliorated atRAL-induced cytotoxicity. Suppression of autophagy quenched mitochondrial ROS and inhibited HO-1 and γ-GCSh expression, indicating that atRAL-activated autophagy enhances intracellular oxidative stress, thereby promoting RPE cell apoptosis. Furthermore, we found that inhibiting endoplasmic reticulum (ER) stress suppressed atRAL-induced mitochondrial ROS generation, subsequently attenuated autophagy and apoptosis in RPE cells.

Conclusion

Taken together, these results suggest that atRAL-induced oxidative stress and ER stress modulate autophagy, which may contribute to RPE degeneration. There may be positive feedback regulatory mechanisms between atRAL-induced oxidative stress and autophagy or ER stress.

References

Lingmin Zhang  1 , Yingying Zhou  1 , Qingqing Xia  1 , Ying Chen  1 , Jie Li  2. All-trans-retinal induces autophagic cell death via oxidative stress and the endoplasmic reticulum stress pathway in human retinal pigment epithelial cells. Toxicol Lett.  322:77-86. Apr 1 2020. doi: 10.1016/j.toxlet.2020.01.005. Epub Jan 10 2020 .