Effect of Shuangdan Mingmu Capsule on Diabetic Retinopathy in Rats via Regulation of miRNAs

PURPOSE: To evaluate the effects of Shuangdan Mingmu (SDMM) capsule on diabetic retinopathy in rats by regulating miRNAs. MATERIALS AND METHODS: Streptozotocin (STZ) (50 mg/kg) was successfully used to induce diabetes in male Sprague-Dawley rats, which were randomly assigned to a group taking SDMM capsules (“diabetic+SDMM”) or a control group (“diabetic”), and the normal group (n=10/group). The diabetic+SDMM capsule group received 1.89g/kg/d of SDMM capsule by gavage, whereas the other groups received the same amount of distilled water. After 12-weeks of gavage, the retina was removed from all rats for histopathological analysis, and miRNA sequencing experiments were carried out to identify the differential expression of miRNAs. These results were then confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: SDMM capsules improved retinal morphology, restored the number of cells in the ganglion cell layer (p<0.0001) and reduced apoptosis in all retinal layers (p values in the outer nuclear layers, inner nuclear layers and ganglion cell layers 0.0001, 0.0147, 0.0034, respectively). In addition, miRNA expression was changed in rats taking SDMM capsules. Compared with the diabetic group, six miRNAs were up-regulated and four miRNAs were down-regulated in the diabetic+SDMM capsule group. The qRT-PCR validation results showed that the expression levels of miR-450b-5p, miR-1249 and miR-155-5p were consistent with the trend of miRNA sequencing results, and were all up-regulated after SDMM capsule treatment. Target gene prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed miRNAs showed that these pathways were mainly concentrated in the focal adhesions and PI3K/Akt, MAPK, and neural factor signaling pathways. CONCLUSION: SDMM capsules may prevent and treat diabetic retinopathy by regulating the expression of miR-450b-5p, miR-1249 and miR-155-5p.