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Jean-Claude P. Jeanny, Laurent Jonet, Marie-Hélène Vesvres, Claire Sergeant, Florian Guillou, Francine F. Behar-Cohen, Courtois Yves, Emilie Picard; Iron Accumulation In Animal Models Of Genetic Retinal Degeneration: Human Transferrin As A Protector For Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6429.
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Retinal degeneration has been associated with iron accumulation in AMD and several rodent models which had one or several iron regulating proteins impairment. We investigated the localization of iron accumulation in rd10 mice and RCS (Royal Collage of Surgeon) rats retina by PIXE (Proton Induced X-ray Emission). Then, we tested the potential neuroprotective effect of human transferrin (hTf), an iron scavenger, on the photoreceptors degeneration.
Eyes from rd10 mice 2, 3 and 4 week-old and RCS rats 35, 45 and 55 day-old and their respective controls were collected. Cryosections of 20µm were laid on Formvar films and aluminium holders and freeze-dried, before analysis. We used PIXE method with a proton microprobe to analyze the iron contents in the retina. The different retinal layers were precisely identified by a post-irradiation staining. To constitutively express human transferrin (hTf) in rd10 mice, we have crossbred rd10 mice with transgenic mice for human transferrin. We also intraperitoneally injected hTf in 5-day-old rd10 mice up to 25 days and in RCS rats from 17 to 55 post-natal days. We compared photoreceptors degeneration by measurement of the outer nuclear layer thickness on histological sections.
First, we demonstrated an iron accumulation in photoreceptor segments dependent of retinal degeneration stages in rd10 mice and RCS rats. At the peak of photoreceptors degeneration (3-weeks), rd10/hTf mice showed less photoreceptors death than rd10 mice. Rods and cones morphologies and photoreceptors segments were preserved. Intraperitoneal injection of hTf in rd10 mice resulted in dose-dependent hTf presence in mice retina. At post-natal 25 days, photoreceptors (both rods and cones) degeneration was considerably reduced at high concentrations of hTf (24-48mg/ml) injected. This protective effect was also seen in 55-day-old RCS rats.
In rd10 mice and RCS rats, which accumulated iron in photoreceptors segments, hTf expressed by genetic modification or intraperitoneally injected permitted to delay photoreceptors degeneration. This study highlights the therapeutical potential of Tf in degenerative diseases like in retinitis pigmentosa or AMD.
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