Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

International Journal of Molecular Sciences

Shang-Chun Tsou¹  Meilin Wang²  Yuan-Yen Chang²  Min-Yen Hsu³  Yai-Ping Hsiao³  Ching-Chung Chen⁴  Hui-Wen Lin⁴  Yi-Ju Lee⁵  Jer-An Lin⁶ 

[1] Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan;Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan;Department of Optometry, Asia University, Taichung 41354, Taiwan;Department of Pathology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 40201, Taiwan;Graduate Institute of Food Safety, National Chung Hsing University, Taichung 40201, Taiwan;

关键词: age-related macular degeneration;    sodium iodate;    human retinal pigment epithelium;    quercetin;    apoptosis;    mitochondrial membrane potential;   

DOI  :  10.3390/ijms22084056

来源: DOAJ

【 摘 要 】

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO₃) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO₃-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO₃-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO₃-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO₃-mediated apoptosis.

【 授权许可】

Unknown