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Antioxidants (Basel). 2019 Mar 27;8(4). pii: E79. doi: 10.3390/antiox8040079.

Suppression of Light-Induced Retinal Degeneration by Quercetin via the AP-1 Pathway in Rats.

Author information

1
Department of Ophthalmology, Faculty of Medicine, Shimane University, Shimane 693-0021, Japan. ykoyama@med.shimane-u.ac.jp.
2
Department of Ophthalmology, Faculty of Medicine, Shimane University, Shimane 693-0021, Japan. kecha@med.shimane-u.ac.jp.
3
Department of Pathology, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA. yongchul.kim.ctr@usuhs.edu.
4
Department of Ophthalmology, Faculty of Medicine, Shimane University, Shimane 693-0021, Japan. aohira@med.shimane-u.ac.jp.
5
Department of Research and Development, Kotobuki Seika Co., Ltd., Tottori 683-0845, Japan. t-ishihara@kozuchi-net.jp.
6
Department of Ophthalmology, Faculty of Medicine, Shimane University, Shimane 693-0021, Japan. mtanito@med.shimane-u.ac.jp.

Abstract

We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine-5'-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.

KEYWORDS:

AP-1; light damage; oxidative stress; quercetin; retina

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