PDF(Pubmed)
Abstract：
Amyloid-beta (Aβ)-related alterations, similar to those found in the brains of patients with Alzheimer\'s disease, have been observed in the retina of patients with glaucoma. Decreased levels of brain-derived neurotrophic factor (BDNF) are believed to be associated with the neurotoxic effects of Aβ peptide. To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ1-40-induced retinal injury in Sprague-Dawley rats, we treated rats by intravitreal administration of phosphate-buffered saline (control), Aβ1-40 (5 nM), or Aβ1-40 (5 nM) combined with BDNF (1 µg/mL). We found that intravitreal administration of Aβ1-40 induced retinal ganglion cell apoptosis. Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ1-40 group than in the control and BDNF groups. In the Aβ1-40 group, low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression. BDNF abolished Aβ1-40-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression. These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ1-40 by activating the BDNF-TrkB signaling pathway in rats.
摘要：
淀粉样β（Aβ）相关改变，类似于在阿尔茨海默病患者的大脑中发现的那些，已在青光眼患者的视网膜中观察到。脑源性神经营养因子（BDNF）水平的降低被认为与Aβ肽的神经毒性作用有关。探讨BDNF对Aβ1-40诱导的SD大鼠视网膜损伤的神经保护作用机制。我们通过玻璃体内施用磷酸盐缓冲盐水（对照）来治疗大鼠，Aβ1-40(5nM),或Aβ1-40（5nM）与BDNF（1µg/mL）组合。我们发现玻璃体内施用Aβ1-40诱导视网膜神经节细胞凋亡。荧光金染色显示Aβ1-40组的视网膜神经节细胞数量明显低于对照组和BDNF组。在Aβ1-40组中，RGCs数量减少与caspase-3表达增加和TrkB和ERK1/2表达减少相关。BDNF消除了Aβ1-40在视网膜中基因和蛋白质水平上诱导的caspase-3表达的增加，并上调了TrkB和ERK1/2的表达。这些发现表明，用BDNF治疗可以通过激活BDNF-TrkB信号通路来防止Aβ1-40诱导的大鼠RGC凋亡。
