自噬
链脲佐菌素
视网膜
内科学
糖尿病性视网膜病变
内分泌学
神经营养因子
视网膜
脑源性神经营养因子
糖尿病
医学
小胶质细胞
化学
生物
炎症
眼科
细胞凋亡
神经科学
受体
生物化学
作者
Maria Consiglia Trotta,Carlo Gesualdo,Hildegard Herman,Sami Gharbia,Cornel Baltă,Caterina Claudia Lepre,Marina Russo,A Itro,Giovanbattista D’Amico,Luisa Peluso,Iacopo Panarese,Gorizio Pieretti,Giuseppe Ferraro,Francesca Simonelli,Michele D’Amico,Silvia Rossi,Anca Hermenean
标识
DOI:10.3390/ijms231710184
摘要
Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25−50−100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome−lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.
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