Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal

Yun Han; Kun-Huan Yang; Dan-Xue He; Chao-Feng Yu; Lei Tao; Chun-Yan Liao; Bin-Xiang Cai; Zu-Guo Liu; Yan Qiu; Ya-Lin Wu

doi:10.18240/ijo.2023.02.04

International Journal of Ophthalmology (Feb 2023)

Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal

Yun Han,
Kun-Huan Yang,
Dan-Xue He,
Chao-Feng Yu,
Lei Tao,
Chun-Yan Liao,
Bin-Xiang Cai,
Zu-Guo Liu,
Yan Qiu,
Ya-Lin Wu

Affiliations

Yun Han: Ya-Lin Wu and Yan Qiu. School of Medicine, Xiamen University, Xiang'an South Road, Xiang'an District, Xiamen 361102, Fujian Province, China. [email protected]; [email protected]
Kun-Huan Yang: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Dan-Xue He: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Chao-Feng Yu: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Lei Tao: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Chun-Yan Liao: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Bin-Xiang Cai: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Zu-Guo Liu: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen 361102, Fujian Province, China
Yan Qiu: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen 361102, Fujian Province, China
Ya-Lin Wu: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen 361102, Fujian Province, China; Shenzhen Research Institute of Xiamen University, Shenzhen 518000, Guangdong Province, China

DOI: https://doi.org/10.18240/ijo.2023.02.04
Journal volume & issue: Vol. 16, no. 2
pp. 191 – 200

Abstract

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AIM: To study the effect of palmitoylethanolamide (PEA) on apoptosis of retinal pigment epithelial (RPE) cells induced by all-trans retinal (atRAL) and to explore the possible molecular mechanism. METHODS: CellTiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) was used to detect the effect of PEA on human-derived retinal epithelial cells (ARPE-19) viability induced by atRAL. A Leica DMi8 inverted microscope was used to observe cell morphology. Reactive oxygen species (ROS) production was evaluated with 2',7'-dichlorodihydrof-luorescein diacetate (H2DCFDA) staining and fluorescence microscopy. Expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), c-Jun, phosphorylated c-Jun (p-c-Jun), Bak, cleaved caspase-3, C/EBP homologous protein (CHOP), and binding (Bip) protein levels were tested by Western blot. Abca4-/-Rdh8-/- mice, mouse models of atRAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration (AMD) and Stargardt disease (STGD1). In the animal models, PEA was injected intraperitoneally. The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice. Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer. Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/- mice was observed by fundus photography. RESULTS: PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS (including mitochondrial ROS) production induced by atRAL. PEA improved the retinal functional, prohibited both RPE and photoreceptor from death, ameliorates light-induced fundus impairment in Abca4-/-Rdh8-/- mice. In vitro and in vivo, PEA inhibited JNK, p-JNK, c-Jun, p-c-Jun, Bak, cleaved caspase-3, CHOP, and Bip protein levels induced by all-trans retinal in ARPE-19 cells. CONCLUSION: PEA has effect on treating RPE cells apoptosis in retinopathy caused by atRAL accumulation. PEA is a potential treatment strategy for dry AMD and STGD1. The molecular mechanism is affecting the ROS-JNK-CHOP signaling pathway partly.

Published in International Journal of Ophthalmology

ISSN: 2222-3959 (Print); 2227-4898 (Online)
Publisher: Press of International Journal of Ophthalmology (IJO PRESS)
Country of publisher: China
LCC subjects: Medicine: Ophthalmology
Website: http://www.ijo.cn/gjyken/ch/index.aspx

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