Retinal degeneration progression changes lentiviral vector cell targeting in the retina.

Détails

Ressource 1Télécharger: BIB_750EC38D5FB4.P001.pdf (1331.89 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_750EC38D5FB4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Retinal degeneration progression changes lentiviral vector cell targeting in the retina.
Périodique
Plos One
Auteur(s)
Calame M., Cachafeiro M., Philippe S., Schouwey K., Tekaya M., Wanner D., Sarkis C., Kostic C., Arsenijevic Y.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Volume
6
Numéro
8
Pages
e23782
Langue
anglais
Résumé
In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/09/2011 14:07
Dernière modification de la notice
08/05/2019 20:29
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