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Light-Induced Retinal Degeneration Correlates with Changes in Iron Metabolism Gene Expression, Ferritin Level, and Aging

Abstract : Purpose: 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.
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Émilie Picard, Isabelle Ranchon-Cole, Laurent Jonet, Carole Beaumont, Francine Behar-Cohen, et al.. Light-Induced Retinal Degeneration Correlates with Changes in Iron Metabolism Gene Expression, Ferritin Level, and Aging. Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2011, 52 (3), pp.1261. ⟨10.1167/iovs.10-5705⟩. ⟨inserm-02983703⟩



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