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

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State: Public
Version: Final published version
Serval ID
serval:BIB_750EC38D5FB4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Retinal degeneration progression changes lentiviral vector cell targeting in the retina.
Journal
Plos One
Author(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
Publication state
Published
Issued date
2011
Volume
6
Number
8
Pages
e23782
Language
english
Abstract
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
Yes
Create date
23/09/2011 13:07
Last modification date
20/08/2019 14:32
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