黄斑变性
成纤维细胞生长因子
视网膜色素上皮
脉络膜
视网膜变性
生物
基因剔除小鼠
视网膜
细胞生物学
医学
内科学
内分泌学
病理
视网膜
眼科
生物化学
神经科学
受体
作者
Tingting Zhao,Wenfei Wang,Kun Gao,Siming Li,Ye Jiang,Zhifeng Yang,Jiannan Liu,Yanli Wang,Shaomin Peng
标识
DOI:10.1016/j.exer.2022.109014
摘要
Age-related macular degeneration (AMD) is the main cause of blindness in elderly individuals. As a metabolic regulator, fibroblast growth factor 21 (FGF-21) has been proven indicated to have an effect on wet AMD, but whether this cytokine has a therapeutic effect on dry AMD is unclear. The current study aimed to evaluate the preventive effects of FGF-21 against retinal degeneration in mice and provide mechanistic insights. FGF-21-/- mice were raised to 10 months of age. Then, the morphological changes in the retinal pigment epithelium (RPE)/choroid of the mice were observed by transmission electron microscopy (TEM), and iTRAQ was used to detect the variations in the protein profile. Next, FGF-21-/- and wild-type mice of the same age were fed hydroquinone to generate a dry AMD mouse model to examine whether exogenous FGF-21 can interfere with the occurrence and development of dry AMD. In vivo studies revealed that following FGF-21 knockout, there was an increase in the expression of complement in the RPE/choroid concomitant with the occurrence of dry AMD-like pathological changes. Furthermore, exogenous FGF-21 administration effectively reversed this phenomenon. FGF-21 also demonstrated strong anti-inflammatory effects in the RPE/choroid by inhibiting the NF-κB pathway. In conclusion, the present study demonstrates that FGF-21 treatment presents a novel therapeutic approach for the prevention and development of dry AMD by reducing complement.
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