Glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa

被引：147
作者：
Sanftner, LHM
Abel, H
Hauswirth, WW
Flannery, JG [1 ]
机构：
[1] Univ Calif Berkeley, Dept Vis Sci, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Neurosci Grp, Berkeley, CA 94720 USA
[3] Univ Florida, Dept Mol Genet, Gainesville, FL 32610 USA
[4] Univ Florida, Dept Microbiol & Ophthalmol, Gainesville, FL 32610 USA
[5] Univ Florida, Powel Gene Therapy Ctr, Gainesville, FL 32610 USA
来源：
MOLECULAR THERAPY | 2001年 / 4卷 / 06期
关键词：
rAAV vector; gene therapy; retinal degeneration; GDNF;
D O I：
10.1006/mthe.2001.0498
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
We designed experiments to evaluate the therapeutic potential of glial cell line derived neurotrophic factor (GDNF) to rescue photoreceptors from genetically determined cell death. Gene transfer of the neurotrophic factor to the retina was achieved via a recombinant adeno-associated virus (rAAV) vector containing the chicken beta -actin promoter/immediate early cytomegalovirus enhancer (CBA) driving the human GDNF gene. We delivered AAV-CBA-GDNF to the retinas of an animal model of retinitis pigmentosa, the TgN S334ter-4 rhodopsin line of transgenic rats. Immunohistochemical studies localized AAV-CBA-GDNF-derived recombinant protein to cell bodies, inner segments, and outer segments of photoreceptor cells as well as to retinal pigment epithelial cells. We assessed the effect of viral delivery by morphometric and electroretinographic analysis. These experiments showed that GDNF vector treatment leads to increased rod photoreceptor survival as indicated by morphometric analysis of outer nuclear layer thickness. AAV-CBA-GDNF-treated retinas also demonstrated functional improvement by the substantially increased amplitude of electroretinograms. AAV-CBA-GDNF delivery had a significant rescue effect on photoreceptor degeneration in this animal model.
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收藏
页码：622 / 629
页数：8
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