• Iron-mediated Retinal Degeneration

    From ironjustice@cool.zzn.com@21:1/5 to All on Mon Oct 12 21:01:53 2015
    Targeting iron-mediated retinal degeneration by local delivery of transferrin. Picard E1, Le Rouzic Q2, Oudar A2, Berdugo M2, El Sanharawi M2, Andrieu-Soler C2, Naud MC2, Jonet L2, Latour C3, Klein C4, Galiacy S5, Malecaze F5, Coppin H3, Roth MP3, Jeanny JC2, Courtois Y2, Behar-Cohen F6.
    Free Radic Biol Med. 2015 Oct 7. pii: S0891-5849(15)00583-3. doi: 10.1016/j.freeradbiomed.2015.08.018.

    Abstract

    Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study,
    therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the
    blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron
    homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of
    hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors
    death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative
    stress.

    Copyright © 2015 Elsevier B.V. All rights reserved.

    KEYWORDS:
    Inflammation; Iron; Neurodegenerative diseases; Neuroprotection; Oxidative stress; Transferrin

    PMID: 26454080

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