期刊
NEUROBIOLOGY OF AGING
卷 30, 期 11, 页码 1865-1876出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2008.01.002
关键词
Iron; Aging; Susceptibility; Neurodegeneration; RGC-5; Stress
资金
- NIH [EY12017]
- Forsythe Foundation
Iron accumulation is associated with age-related neurodegenerations and may contribute to age-related increased susceptibility of neurons to damage. We compared young and old rodent retinas to assess iron homeostasis during normal aging and the effects of increased iron on the susceptibility of retinal neurons to degeneration. Retinal iron was significantly increased with age. Quantitative RT-PCR showed that transferrin and ferritin genes were upregulated in the aged retina. At the protein level, we found decreased transferrin, and increased transferrin receptor, ferritin, ferroportin, and ceruloplasmin in the aged retina. These results support an increased steady state of iron with age in the retina. We tested susceptibility of retinal neurons with increased intracellular iron to damage in vitro. Exposure of RGC-5 cells to increased iron potentiated the neurotoxicity induced by paraquat, glutamate, and TNF alpha. Our results demonstrate that iron homeostasis in the retina is altered with age and suggest that iron accumulation, due to altered levels of iron-regulatory proteins in the aged retina, could be a susceptibility factor in age-related retinal diseases. (C) 2008 Elsevier Inc. All rights reserved.
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