Gene therapy has been proposed as a feasible strategy for RGC survival and optic nerve regeneration. Some preclinical and clinical studies revealed intraocular inflammation after intravitreal injection of adeno-associated virus (AAV) by slit-lamp or indirect ophthalmoscope. Here we evaluate the longitudinal profile of immediate inflammatory responses after AAV2 injection in rat retina and vitreous body by optical coherence tomography (OCT). Adult Fischer F344 rats were intravitreally injected once with saline, AAV2 or zymosan. Retinal thickness and cell infiltration were recorded by OCT longitudinally for 2 months and verified by histological analysis. The transduction rate of single intravitreal AAV2 injection was 21.3 ± 4.9% of whole retina, and the transduction efficiency on RGCs was 91.5 ± 2.5% in the transduced area. Significant increase in cell infiltration was observed from Day 1-3 after AAV2 injection, compared to very few infiltrating cells observed in the saline-injected group. The infiltrating cells ceased at Day 5 after intravitreal injection and remained absent at 2 months. The thicknesses of total and inner retina were increased along Day 1-3 after AAV2 injection, but reverted to normal afterwards. The surviving RGCs in the AAV2-injected groups at Day 14 showed no significant difference compared to saline-injected group. In summary, this study revealed the immediate inflammatory responses and retinal edema after intravitreal AAV2 injection in normal rats, without influencing long-term retinal thickness and RGC survival. OCT can be implemented for the time-lapse in vivo evaluation of inflammatory response after AAV-mediated gene therapy through intravitreal injection.

中文翻译：

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通过光学相干断层扫描对大鼠玻璃体内注射AAV2后的即时炎症反应进行纵向评估。

已经提出基因疗法作为RGC存活和视神经再生的可行策略。一些临床前和临床研究表明，通过裂隙灯或间接检眼镜在玻璃体内注射腺相关病毒（AAV）后眼内发炎。在这里，我们通过光学相干断层扫描（OCT）评价大鼠视网膜和玻璃体中AAV2注射后即时炎症反应的纵向分布。成年Fischer F344大鼠玻璃体内注射盐水，AAV2或酵母聚糖。通过OCT纵向记录2个月的视网膜厚度和细胞浸润，并通过组织学分析证实。单次玻璃体内注射AAV2的转导率为整个视网膜的21.3±4.9％，在转导区域，RGC的转导效率为91.5±2.5％。与注射盐水的组中观察到的极少数浸润细胞相比，从注射AAV2后的第1-3天开始观察到细胞浸润的显着增加。玻璃体内注射后第5天，浸润细胞停止，并在2个月时消失。AAV2注射后第1-3天，总视网膜厚度和内部视网膜厚度增加，但随后恢复正常。与注射盐水的组相比，在第14天注射AAV2的组中存活的RGC表现出无显着差异。总之，这项研究揭示了正常大鼠玻璃体内注射AAV2后立即产生的炎症反应和视网膜水肿，而没有影响长期的视网膜厚度和RGC存活率。