Induction of amyloid precursor protein by the neurotoxic peptide, amyloid-beta 25-35, causes retinal ganglion cell death

Abstract

Patients with Alzheimer's disease (AD) show a significantly increased incidence of glaucoma. AD is also associated with the occurrence of the neurotoxic peptide amyloid beta (Aβ). Therefore, we investigated whether Aβ is associated with retinal cell death in a retinal ganglion cell line (RGC-5). Treatment with Aβ25-35, a neurotoxic fragment of Aβ, induced cell death in RGC-5 in both a concentration- and time-dependent manner. The amount of amyloid precursor protein was increased by treatment of RGC-5 and primary culture of mouse cortical neurons with fibril Aβ25-35 and Aβ1-42, which is a putative physiological neurotoxic fragment of Aβ present in AD. Amyloid precursor protein knockdown inhibited the cell death induced by Aβ25-35. Treatment with Aβ25-35 increased the amount of intracellular Aβ1-40 and Aβ1-42, while β- and γ-secretase inhibitors reduced cell death. Thus, the regulation of Aβ can be viewed as a new therapeutic target for glaucoma, especially in patients with coincident AD. © 2010 International Society for Neurochemistry.