Changes in iron-regulatory proteins in the aged rodent neural retina.
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 TNFalpha. 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.
Chen
Huiyi
H
The Forsythe Laboratory for Investigation of Aging Retina, Department of Ophthalmology, Northwestern University School of Medicine, Tarry 13-753, 303 East Chicago Avenue, Chicago, IL 60611, United States. huiyi-chen@northwestern.edu
Liu
Bin
B
Lukas
Thomas J
TJ
Suyeoka
Genn
G
Wu
Grace
G
Neufeld
Arthur H
AH
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival; D002570:Ceruloplasmin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D064451:Hepcidins; D007501:Iron / Q000097:blood; D035925:Iron-Regulatory Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000494:pharmacology; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D005290:Ferric Compounds; D064451:Hepcidins; D035925:Iron-Regulatory Proteins; D009153:Mutagens; D011990:Receptors, Transferrin; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin; D007501:Iron; D002570:Ceruloplasmin; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate