Retinal degeneration progression changes lentiviral vector cell targeting in the retina.
Retinal degeneration progression changes lentiviral vector cell targeting in the retina.
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DOI：
10.1371/journal.pone.0023782
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Arsenijevic Y
中科院分区：
文献类型：
--
作者：
Calame M;Cachafeiro M;Philippe S;Schouwey K;Tekaya M;Wanner D;Sarkis C;Kostic C;Arsenijevic Y
在正常小鼠中，慢病毒载体（LV）可以非常有效地靶向RPE细胞，但只有在发育过程中才能很好地转导视网膜神经元。在本研究中，我们研究了LV在小鼠视网膜变性中的趋向性，我们知道视网膜在变性过程中会发生结构变化。我们假设外限制膜（OLM）的改变会增加病毒转导。使用VSVG和Mokola包膜测试了两种不同的LV假型，以及两种视网膜变性动物模型：光损伤Balb-C和Rhodopsin敲除（Rho-/-）小鼠。光损伤后，OLM发生改变，LV-VSVG-Rhop-GFP载体的转导光感受器数量没有明显增加。在Rho-/-小鼠中，也观察到OLM的改变，但转导光感受器的可能性降低，可能是由于持续的胶质瘤。无所不在的启动子的使用允许更好的光感受器转导，这表明光感受器特异性启动子活性在光感受器变性的晚期发生变化。然而，目标光感受器的数量仍然很低。相反，具有Mokola包膜的LV假型允许载体广泛分散到视网膜（对应于注射泡），优先靶向<s:1> ller细胞，这种情况在野生型视网膜中不会发生。莫科拉假型慢病毒载体可用于改造这些胶质细胞，将分泌的治疗因子输送到视网膜病变区域。
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.
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影响因子：
25
作者：
Kinouchi, R;Takeda, M;Chen, DF
通讯作者：
Chen, DF
RPE65的慢病毒基因转移在Leber先天性amurosis小鼠模型中挽救了锥体的生存和功能。
影响因子：
15.8
作者：
Bemelmans, Alexis-Pierre;Kostic, Corinne;Crippa, Sylvain V.;Hauswirth, William W.;Lem, Janis;Munier, Francis L.;Seeliger, Mathias W.;Wenzel, Andreas;Arsenijevic, Yvan
通讯作者：
Arsenijevic, Yvan
影响因子：
4.4
作者：
Greenberg, Kenneth P.;Geller, Scott F.;Flannery, John G.
通讯作者：
Flannery, John G.
影响因子：
3.4
作者：
Campbell, M.;Humphries, M.;Brankin, B.
通讯作者：
Brankin, B.
影响因子：
6.2
作者：
Colin, Angelique;Faideau, Mathilde;Deglon, Nicole
通讯作者：
Deglon, Nicole