Genipin protects against mitochondrial damage of the retinal pigment epithelium under hyperglycemia through the pathway mediated by the signaling axis.

BACKGROUND

To investigate the protective effect and mechanism of genipin (GE) on mitochondrial damage in retinal pigment epithelial (RPE) cells induced by high glucose.

METHODS

Differential genes of GE in the treatment of diabetic retinopathy (DR) were screened by the Gene Expression Omnibus (GEO) database. Differential genes located in the pathway were obtained. TargetScan, miRDB, and DIANA databases were used to predict the targeted microRNAs (miRNAs) of differential genes. A high-fat diet combined with streptomycin (STZ) intraperitoneal injection were used to establish a diabetic mouse model. Diabetic mice were treated with GE by intragastric administration. The functional and molecular changes of the retina were detected by electroretinogram (ERG) and reverse transcription-polymerase chain reaction (RT-PCR). ARPE-19 cells were cultured under hyperglycemic conditions with and inhibitors. was knocked down/overexpressed to detect changes in cell function, activity, and mitochondrial function. The dual luciferase reporter assay confirmed the targeted binding of with

RESULTS

Bioinformatics analysis finally yielded as the research target gene. was predicted to be the targeted miRNA of by online databases. The results of animal experiments showed that the retinal function of mice recovered after GE administration (P<0.05), the expression of and in RPE cells was significantly increased (P<0.05), and the expression of was significantly decreased (P<0.05). The results of cell experiments showed that the functions of cells and mitochondria recovered after the addition of GE under hyperglycemia (P<0.05). Cell and mitochondrial functions were decreased after the addition of inhibitor (P<0.05). Overexpression of or inhibition of increased cell activity and mitochondrial function (P<0.05). The results of the dual luciferase reporter assay showed that had a targeted binding site with

CONCLUSIONS

GE protects ARPE-19 cell functional activity, inflammatory responses, and mitochondrial damage by promoting the signaling pathway and regulating the expression of the / signaling axis.