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.

Key words: amyloid-beta 1–40, brain-derived neurotrophic factor, Fluoro-Gold, neuroprotection, retinal ganglion cells (RGC), retinal toxicity, tropomyosin receptor kinase B (TrkB)