Abstract
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 TNFα. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1865-1876 |
| Number of pages | 12 |
| Journal | Neurobiology of Aging |
| Volume | 30 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2009 |
Funding
This work was supported by NIH grant EY12017 and a generous gift from the Forsythe Foundation. The authors thank Neeraj Agarwal of the University of North Texas Health Science Center for providing the RGC-5 cell line.
Keywords
- Aging
- Iron
- Neurodegeneration
- RGC-5
- Stress
- Susceptibility
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Aging
- General Neuroscience
- Developmental Biology