Abstract
Purpose: :
Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Many stimuli such as oxidative stress, ischemia, glutamate, and endoplasmic reticulum (ER) stress are reported to initiate the retina cell death. Recently, it has been reported that patients with Alzheimer’s disease (AD) significantly increased an occurrence rate of glaucoma. Amyloid beta (Aβ) is known as a neurotoxic peptide which is one of the pathogenesis of AD. Hence, it is assumed that Aβ leads to not only neuronal cell death in AD patients but also the retinal cell death in glaucoma patients. The purpose of this study is to confirm whether the retinal cell death is caused by Aβ and to elucidate the retinal cell death mechanism.
Methods: :
We investigated whether Aβ causes the retinal cell death using retinal ganglion cell (RGC-5). RGC-5 were treated with 5-20 µM of Aβ (25-35) oligomer for 12 to 48 h. The cells were stained using Hoechst 33324 and propidium iodide, and then counted to measure cell death. Simultaneously, the cells were collected and analyzed by western blotting and Real-Time PCR methods. The cells were also transfected with amyloid precursor protein (APP) siRNA to investigate whether APP influence the cell death by Aβ.
Results: :
Treatment of Aβ (25-35) oligomer induced cell death in RGC-5 in concentration- and time-dependent manners. Interestingly, we found that the amount of APP protein was simultaneously increased by Aβ treatment in RGC-5.
Conclusions: :
Although the mechanism of APP induction remains unclear, these findings may be new therapeutic targets for glaucoma, especially the patients with coincidence of AD.
Keywords: apoptosis/cell death • retinal degenerations: cell biology • ganglion cells