Ola Mohammad S, Ahmed M M, Shams Shakeeb, Al-Rejaie Salim S
Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Saudi J Biol Sci. 2017 Sep;24(6):1186-1194. doi: 10.1016/j.sjbs.2016.11.017. Epub 2016 Dec 3.
Diabetic retinopathy (DR) is a severe complication of diabetes and the leading cause of blindness among working adults worldwide. DR is being widely recognized as a neurodegenerative disease of the retina, since, retinal neurons are damaged soon after diabetes onset. Diabetes-induced oxidative stress is considered as central factor that dysregulates neurotrophic factors and activates apoptosis, thereby damages neurons in the diabetic retina. Flavonoids being a powerful antioxidant have been considered to protect neurons in diabetic retina. The purpose of this study was to analyze the beneficial effects of flavonoid, quercetin to protect neurons in the diabetic rat retina. We quantitated the expression levels of BDNF, NGF, TrkB, synaptophysin, Akt, Bcl-2, cytochrome c and caspase-3 using Western blotting techniques in the diabetic retina with and without quercetin treatments and compared with non-diabetic rats. In addition, we employed ELISA techniques to determine the level of BDNF. Caspase-3 activity and the level of glutathione were analyzed by biochemical methods. Our results indicate that quercetin treatment to diabetic rats caused a significant increase in the level of neurotrophic factors and inhibited the level of cytochrome c and caspase-3 activity in the diabetic retina. Furthermore, the level of an anti-apoptotic protein Bcl-2 was augmented in quercetin treated diabetic retina. Thus, quercetin, may protect the neuronal damage in diabetic retina by ameliorating the levels of neurotrophic factors and also by inhibiting the apoptosis of neurons. Therefore, this study suggests that quercetin can be a suitable therapeutic agent to prevent neurodegeneration in diabetic retinopathy.
糖尿病视网膜病变（DR）是糖尿病的一种严重并发症，也是全球在职成年人失明的主要原因。DR被广泛认为是一种视网膜神经退行性疾病，因为糖尿病发病后不久视网膜神经元就会受损。糖尿病诱导的氧化应激被认为是调节神经营养因子失调并激活细胞凋亡的核心因素，从而损害糖尿病视网膜中的神经元。黄酮类化合物作为一种强大的抗氧化剂，被认为可以保护糖尿病视网膜中的神经元。本研究的目的是分析黄酮类化合物槲皮素对糖尿病大鼠视网膜神经元的保护作用。我们使用蛋白质印迹技术定量分析了在有或没有槲皮素处理的糖尿病视网膜中脑源性神经营养因子（BDNF）、神经生长因子（NGF）、酪氨酸激酶受体B（TrkB）、突触素、蛋白激酶B（Akt）、B细胞淋巴瘤/白血病-2（Bcl-2）、细胞色素c和半胱天冬酶-3的表达水平，并与非糖尿病大鼠进行比较。此外，我们采用酶联免疫吸附测定（ELISA）技术测定BDNF水平。通过生化方法分析半胱天冬酶-3的活性和谷胱甘肽水平。我们的结果表明，对糖尿病大鼠进行槲皮素处理可使神经营养因子水平显著升高，并抑制糖尿病视网膜中细胞色素c的水平和半胱天冬酶-3的活性。此外，在槲皮素处理的糖尿病视网膜中，抗凋亡蛋白Bcl-2的水平升高。因此，槲皮素可能通过改善神经营养因子水平以及抑制神经元凋亡来保护糖尿病视网膜中的神经元损伤。因此，本研究表明槲皮素可能是预防糖尿病视网膜病变神经退行性变的合适治疗药物。
