Brain-derived neurotrophic factor gene delivery to muller glia preserves structure and function of light-damaged photoreceptors
Brain-derived neurotrophic factor gene delivery to muller glia preserves structure and function of light-damaged photoreceptors
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DOI：
10.1167/iovs.05-0362
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Di Polo, A
中科院分区：
文献类型：
--
作者：
Gauthier, R;Joly, S;Di Polo, A
目的。检验腺病毒 (Ad) 介导的脑源性神经营养因子 (BDNF) 向 Muller 细胞的基因传递可以保护光感受器免受光诱导的视网膜变性的假设。方法。成年 Sprague-Dawley 大鼠接受眼内注射 Ad。 BDNF，含有绿色荧光蛋白（GFP）基因的对照Ad，或BDNF重组蛋白。然后将动物暴露于持续光照 5、10 或 16 天。广告的效果。通过测量外核层 (ONL) 厚度，从组织学角度检查 BDNF 对光感受器存活的影响，并通过测量视网膜电图 (ERG) 反应，从功能角度检查 BDNF 对光感受器存活的影响。 结果。广告。 BDNF 介导 Muller 细胞生物活性神经营养素的持续表达，这种表达在病毒载体施用后持续至少 30 天。将 BDNF 基因传递至米勒神经胶质细胞可显着提高光损伤光感受器的存活率和结构完整性。例如，暴露于光 10 天后，接受 Ad 的眼睛的上中央视网膜中 ONL 保留的平均百分比。 BDNF 为 71%，而接受对照 Ad 的眼睛为 46%。对侧眼 GFP 或 15%。重要的是，视网膜暴露在广告中。 BDNF 比接受单次眼内注射 BDNF 重组蛋白的视网膜具有更多的光感受器核。 Ad的神经保护作用。 BDNF 伴随着治疗眼睛的 ERG 反应的保留。结论。这些数据证明了将 BDNF 基因转移到 Muller 细胞中是在视网膜变性中保留光感受器结构和功能的有效策略。
PURPOSE. To test the hypothesis that adenovirus (Ad)-mediated gene delivery of brain-derived neurotrophic factor ( BDNF) to Muller cells can protect photoreceptors from light-induced retinal degeneration.METHODS. Adult Sprague-Dawley rats received an intraocular injection of Ad. BDNF, control Ad containing the green fluorescent protein (GFP) gene, or BDNF recombinant protein. Animals were then exposed to 5, 10, or 16 days of constant light. The effect of Ad. BDNF on photoreceptor survival was examined histologically, by measuring the outer nuclear layer (ONL) thickness, and functionally, by measuring the electroretinographic ( ERG) response.RESULTS. Ad. BDNF mediated sustained expression of bioactive neurotrophin by Muller cells that lasted for at least 30 days after viral vector administration. BDNF gene delivery to Muller glia markedly increased the survival and structural integrity of light-damaged photoreceptors. For example, after 10 days of exposure to light, the average percentage of ONL preservation in the superior central retina of eyes that received Ad. BDNF was 71%, compared with 46% in eyes that received a control Ad. GFP or 15% in contralateral eyes. Of importance, retinas exposed to Ad. BDNF had more photoreceptor nuclei than retinas that received a single intraocular injection of BDNF recombinant protein. The neuroprotective effect of Ad. BDNF was accompanied by preservation of the ERG response of the treated eyes.CONCLUSIONS. These data provide proof of the concept that BDNF gene transfer into Muller cells is an effective strategy for preserving structure and function of photoreceptors in retinal degeneration.