Targeting iron-mediated retinal degeneration by local delivery of transferrin.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_D77ED06BE30E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeting iron-mediated retinal degeneration by local delivery of transferrin.
Journal
Free Radical Biology and Medicine
Author(s)
Picard E., Le Rouzic Q., Oudar A., Berdugo M., El Sanharawi M., Andrieu-Soler C., Naud M.C., Jonet L., Latour C., Klein C., Galiacy S., Malecaze F., Coppin H., Roth M.P., Jeanny J.C., Courtois Y., Behar-Cohen F.
ISSN
1873-4596 (Electronic)
ISSN-L
0891-5849
Publication state
Published
Issued date
12/2015
Peer-reviewed
Oui
Volume
89
Pages
1105-1121
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
Animals, Cells, Cultured, Disease Models, Animal, Homeostasis/drug effects, Immunoenzyme Techniques, Inflammation/chemically induced, Inflammation/prevention & control, Iron/toxicity, Male, Mice, Oxidative Stress/drug effects, RNA, Messenger/genetics, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Retinal Degeneration/chemically induced, Retinal Degeneration/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transferrin/pharmacology
Pubmed
Web of science
Create date
10/02/2015 9:56
Last modification date
20/08/2019 15:57
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