Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants.
Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants.
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DOI：
10.1371/journal.pone.0035318
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kalatzis V
中科院分区：
文献类型：
--
作者：
Hippert C;Ibanes S;Serratrice N;Court F;Malecaze F;Kremer EJ;Kalatzis V
角膜是透明的无血管组织，充当眼睛的主要屈光表面。由内基质保证的角膜透明度对于这一作用至关重要。某些遗传性或获得性疾病可能会导致基质透明度破坏。结果，进入眼睛的光线被阻挡或扭曲，导致视力下降。恢复透明度的可能治疗方法是通过基于病毒的基因疗法。由于其免疫豁免性质和低周转率，基质特别适合这种策略。我们在小鼠角膜基质内注射和人类外植体离体注射后，测定了 AAV 载体转导角膜细胞的潜力。在小鼠和人类角膜中，我们使用单次注射转导了整个基质，优先靶向角膜细胞，并实现了长期基因转移（在小鼠体内长达 17 个月）。在测试的血清型中，AAV2/8 最有希望在小鼠和人类中进行基因转移。此外，在角膜受到攻击后，转基因表达可能会短暂增加。
The cornea is a transparent, avascular tissue that acts as the major refractive surface of the eye. Corneal transparency, assured by the inner stroma, is vital for this role. Disruption in stromal transparency can occur in some inherited or acquired diseases. As a consequence, light entering the eye is blocked or distorted, leading to decreased visual acuity. Possible treatment for restoring transparency could be via viral-based gene therapy. The stroma is particularly amenable to this strategy due to its immunoprivileged nature and low turnover rate. We assayed the potential of AAV vectors to transduce keratocytes following intra-stromal injection in vivo in the mouse cornea and ex vivo in human explants. In murine and human corneas, we transduced the entire stroma using a single injection, preferentially targeted keratocytes and achieved long-term gene transfer (up to 17 months in vivo in mice). Of the serotypes tested, AAV2/8 was the most promising for gene transfer in both mouse and man. Furthermore, transgene expression could be transiently increased following aggression to the cornea.
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