Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal...

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 Aβ_1-40-induced retinal injury in Sprague-Dawley rats, we treated rats by intravitreal administration of phosphate-buffered saline (control), Aβ_1-40 (5 nM), or Aβ_1-40 (5 nM) combined with BDNF (1 µg/mL). We found that intravitreal administration of Aβ_1-40 induced retinal ganglion cell apoptosis. Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_1-40 group than in the control and BDNF groups. In the Aβ_1-40 group, low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression. BDNF abolished Aβ_1-40-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 Aβ_1-40 by activating the BDNF-TrkB signaling pathway in rats.