Abstract
This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.