Beta-amyloid (A beta) derived from amyloid precursor protein (APP) has been associated with retinal degeneration in Alzheimer's disease (AD) and glaucoma. This study examined whether hypoxia exposure induces A beta accumulation in RGC-5 cells. While levels of APP mRNA and protein significantly increased in the cells, elevated abundance of A beta was also observed in cells and culture medium between 12 or 24 and 48 h after 5% O-2 hypoxia treatment. Additionally, there is a close relationship between induction of APP and A beta and intracellular accumulation of ROS along with loss of mitochondrial membrane potential followed by the death of RGC-5 cells in culture under hypoxia. These results suggest a possible involvement of APP and A beta in the death of RGCs challenged by hypoxia. (C) 2011 Elsevier Inc. All rights reserved.