Overexpressed or intraperitoneally injected human transferrin prevents photoreceptor degeneration in rd10 mice.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_7C5D5BD8F500
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Overexpressed or intraperitoneally injected human transferrin prevents photoreceptor degeneration in rd10 mice.
Périodique
Molecular Vision
Auteur⸱e⸱s
Picard E., Jonet L., Sergeant C., Vesvres M.H., Behar-Cohen F., Courtois Y., Jeanny J.C.
ISSN
1090-0535 (Electronic)
ISSN-L
1090-0535
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
16
Pages
2612-2625
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
PURPOSE: Retinal degeneration has been associated with iron accumulation in age-related macular degeneration (AMD), and in several rodent models that had one or several iron regulating protein impairments. We investigated the iron concentration and the protective role of human transferrin (hTf) in rd10 mice, a model of retinal degeneration.
METHODS: The proton-induced X-ray emission (PIXE) method was used to quantify iron in rd10 mice 2, 3, and 4 weeks after birth. We generated mice with the β-phosphodiesterase mutation and hTf expression by crossbreeding rd10 mice with TghTf mice (rd10/hTf mice). The photoreceptor loss and apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling in 3-week-old rd10/hTf mice and compared with 3-week-old rd10 mice. The neuroprotective effect of hTf was analyzed in 5-day-old rd10 mice treated by intraperitoneal administration with hTf for up to 25 days. The retinal hTf concentrations and the thickness of the outer nuclear layer were quantified in all treated mice at 25 days postnatally.
RESULTS: PIXE analysis demonstrated an age-dependent iron accumulation in the photoreceptors of rd10 mice. The rd10/hTf mice had the rd10 mutation, expressed high levels of hTf, and showed a significant decrease in photoreceptor death. In addition, rd10 mice intraperitoneally treated with hTf resulted in the retinal presence of hTf and a dose-dependent reduction in photoreceptor degeneration.
CONCLUSIONS: Our results suggest that iron accumulation in the retinas of rd10 mutant mice is associated with photoreceptor degeneration. For the first time, the enhanced survival of cones and rods in the retina of this model has been demonstrated through overexpression or systemic administration of hTf. This study highlights the therapeutic potential of Tf to inhibit iron-induced photoreceptor cell death observed in degenerative diseases such as retinitis pigmentosa and age-related macular degeneration.
Mots-clé
Animals, Biological Transport/drug effects, Disease Models, Animal, Electron Probe Microanalysis, Humans, Injections, Intraperitoneal, Iron/metabolism, Mice, Retina/drug effects, Retina/metabolism, Retinal Cone Photoreceptor Cells/drug effects, Retinal Cone Photoreceptor Cells/metabolism, Retinal Degeneration/drug therapy, Retinal Degeneration/pathology, Retinal Rod Photoreceptor Cells/drug effects, Retinal Rod Photoreceptor Cells/metabolism, Spectrometry, X-Ray Emission, Transferrin/administration & dosage, Transferrin/pharmacology
Pubmed
Web of science
Création de la notice
23/08/2013 8:15
Dernière modification de la notice
20/08/2019 15:37
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