Light-induced retinal degeneration correlates with changes in iron metabolism gene expression, ferritin level, and aging.
OBJECTIVE
Retinal degeneration is associated with iron accumulation in several rodent models in which iron-regulating proteins are impaired. Oxidative stress is catalyzed by unbound iron.


METHODS
The role of the heavy chain of ferritin, which sequesters iron, in regulating the thickness of the photoreceptor nuclear layer in the 4- and 16-month-old wild-type H ferritin (HFt(+/+)) and heterozygous H ferritin (HFt(+/-)) mice was investigated, before and 12 days after exposure to 13,000-lux light for 24 hours. The regulation of gene expression of the various proteins involved in iron homeostasis, such as transferrin, transferrin receptor, hephaestin, ferroportin, iron regulatory proteins 1 and 2, hepcidin, ceruloplasmin, and heme-oxygenase 1, was analyzed by quantitative (q)RT-PCR during exposure (2, 12, and 24 hours) and 24 hours after 1 day of exposure in the 4-month-old HFt(+/+) and HFt(+/-) mouse retinas.


RESULTS
Retinal degeneration in the 4-month-old HFt(+/-) mice was more extensive than in the HFt(+/+) mice. Yet, it was more extensive in both of the 16-month-old mouse groups, revealing the combined effect of age and excessive light. Injury caused by excessive light modified the temporal gene expression of iron-regulating proteins similarly in the HFt(+/-) and HFt(+/+) mice.


CONCLUSIONS
Loss of one allele of H ferritin appears to increase light-induced degeneration. This study highlighted that oxidative stress related to light-induced injury is associated with major changes in gene expression of iron metabolism proteins.
Picard
Emilie
E
Institut National de la Santé et de la Recherche Médicale, U872, Paris, France. picardemilie@gmail.com
Ranchon-Cole
Isabelle
I
Jonet
Laurent
L
Beaumont
Carole
C
Behar-Cohen
Francine
F
Courtois
Yves
Y
Jeanny
Jean-Claude
JC
D000375:Aging / Q000502:physiology*; D000818:Animals; D001052:Apoferritins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics*; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D012333:RNA, Messenger; D001052:Apoferritins; D007501:Iron