Gastrodin ameliorates oxidative stress-induced RPE damage by facilitating autophagy and phagocytosis through PPARα-TFEB/CD36 signal pathway

被引:2
|
作者
Wen, Chaojuan [1 ]
Yu, Xinyue [1 ]
Zhu, Jingya [1 ]
Zeng, Jingshu [1 ]
Kuang, Xielan [1 ,2 ]
Zhang, Youao [1 ]
Tang, Shiyu [1 ]
Zhang, Qingjiong [1 ]
Yan, Jianhua [1 ]
Shen, Huangxuan [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou 510060, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Eye Biobank, Guangzhou 510060, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastrodin; Age-related macular degeneration (AMD); Oxidative stress; Autophagy; Phagocytosis; MACULAR DEGENERATION; 4-HYDROXYNONENAL; 4-HNE; PATHOPHYSIOLOGY; CELLS;
D O I
10.1016/j.freeradbiomed.2024.08.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPAR alpha-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPAR alpha and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease.
引用
收藏
页码:103 / 116
页数:14
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