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

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