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E. Picard, I. Ranchon-Cole, L. Jonet, C. Beaumont, J.-C. Jeanny, F. Behar-Cohen, Y. Courtois; H-Ferritin and Photoreceptors Protection After Light Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4392.
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Altered iron homeostasis is associated with AMD. Ferritin (Ft) which controls the labile iron pool (LIP) is increased in AMD patient retina. Ft is a heteropolymer composed of two chains, H and L. The H chain carries a ferroxidase center, essential for iron incorporation and oxidation of ferrous iron. To determine the role of HFt in iron regulation and under oxidative stress condition, we have used mice heterozygous for the H chain of Ferritin (HFt+/-) (C. Beaumont), and induced photoreceptors (PR) degeneration by light injury.
We have studied histology and H and L-Ft immunoreactivity in the retina from HFt+/- and HFt+/+ control mice (genetic background Balb/C) at two stages, 3-4 and 16-18 months. Then, we exposed mice to white light (13000 lux) for 24 hours (I. Ranchon-Cole) and compared the light sensitivity of HFt+/- to control mice by measurement of outer nuclear layer (ONL) thickness. Iron regulation proteins and oxidative stress markers were also analysed, by RT-qPCR and ELISA assay, on illuminated mice retina.
There were no histological differences in the retina between HFt+/- and control mice aged 4 and 18 months respectively. HFt and LFt were localised in the inner segments of the PR, outer plexiform layer, inner nuclear layer and ganglion cell layer. Compared to control, HFt expression in HFt+/- mice retina was reduced and LFt expression was higher at both stages. In condition of light exposure, 3 months old HFt+/- mice showed a diminution (28%) of ONL thickness compared to control. However, at 16 months, HFt+/- and control illuminated mice present a similar huge decrease in ONL thickness.
Mice heterozygous for HFt allowed us to explore the mechanisms of iron regulation in stress condition. Young adult mice HFt+/-, which had 50% less of HFt expression, were more sensitive to light injury than control. The same PR sensitivity in old mice from both types suggested that, even in HFt+/+ retina, Ft could not control iron accumulation resulting from ageing and photo-oxidative stress. Moreover, the upregulation of L-Ft expression was not sufficient to prevent this sensitivity. Ferritin is one of the proteins involved in the fine-tuning of LIP in the retina. The comprehension of retinal iron regulation is a first step for developing therapeutical neuroprotection strategies in ageing or AMD.
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