Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection

Abstract

Background: Chronic diabetic retinopathy (DR) is a diabetic complication that causes blindness. Brainderived neurotrophic factor (BDNF) expression is induced by fluoxetine. We observed the effects of fluoxetine on a streptozotocin (STZ)-induced diabetic rat model in this study. Materials and Methods: Rats were divided into three groups: Control, diabetic (65 mg/kg STZ injection), and diabetic with fluoxetine injection (20 mg/kg/week, six times). Western blotting was performed using anti-BDNF and anti-hexaribonucleotide-binding protein-3. Expression of BCL2 apoptosis regulator-like protein 11 (BIM) was analysed using a reverse transcription-polymerase chain reaction. Results: BDNF levels were significantly higher in the diabetic group treated with fluoxetine than in the untreated diabetic group. BIM expression was higher in the diabetic group than in the control group. BIM gene expression was lower in fluoxetinetreated diabetic group than in the untreated diabetic group. Conclusion: Fluoxetine had an anti-apoptotic effect with upregulation of BDNF expression in retina of rats with STZinduced diabetes.Diabetic retinopathy (DR) is a complication of diabetes that causes blindness (1). Important mechanisms of blindness are macular edema and alteration of neovascularisation (2, 3). Vascular endothelial growth factor (VEGF) is the most effective mediator of DR progression (4). Anti-VEGF effects are associated with the regression of retinal neovascularisation (5) and anti-VEGF treatment is the most effective approach for DR therapy. However, some patients show poor response to this treatment (6). Thus, comprehension of the pathogenesis of DR is critical. Although DR is traditionally known as a vascular disease, some studies have shown that neuronal pathological changes occur in the retina, including physiological and structural alterations (7, 8).Brain-derived neurotrophic factor (BDNF) is a neuroprotective growth factor that affects neuronal cell proliferation and survival (9). BDNF binds to tropomyosin receptor kinase B (TRKB), which leads to nerve cell survival, repair, and development through the neurotrophic signalling pathway (10). BDNF has also been observed in retinal neuronal cells. BDNF is expressed in retinal ganglion cells (RGCs) and was found to play an important role in their survival in rats with streptozotocin (STZ)-induced diabetes (11). Cusato et al. reported that BDNF prevented cell death in the inner nuclear layer of the retina (12). Uzel et al. showed that BDNF is a good marker for the early diagnosis of DR (13).In a previous study, BDNF expression was induced by fluoxetine, a selective inhibitor of serotonin reuptake, to treat major depression (14). In this study, we analysed the expression of BDNF and BCL2 apoptosis regulator-like protein 11 (BIM) after fluoxetine injection in the STZinduced diabetes rat model to investigate the effect of fluoxetine on BDNF signalling. Materials and MethodsRat model of DR. All animal studies were approved by the Chosun University Institutional Animal Care and Use C...

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“…Western blot analysis. Western blotting was performed at three and fourteen days after BCCAO, as previously described (15). Brains of rats in the ligated bi-carotid artery group and no surgery group were extracted using anesthesia (sevoflurane 1.0-2.0%, end-tidal concentration).…”

Cell and molecular targeted therapies for diabetic retinopathy

“…Remarkably, a high molecular weight protein like NGF can be transported from the anterior to the posterior segment to reach the retina and optic nerve, providing protection Serum and aqueous humor levels of BDNF were significantly lower in diabetes mellitus patients before DR development ( 131 ). Additionally, BDNF levels were significantly reduced in the retina of DR rats ( 132 , 133 ). BDNF protects against neurodegeneration in DR, and the neuroprotection and Müller cell viability it offers are mediated by VEGF ( 134 ).…”