Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs
Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs
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DOI：
10.1007/s10633-005-3159-0
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发表时间：
2005-07-01
影响因子：
1.4
通讯作者：
Seeliger, M
中科院分区：
文献类型：
--
作者：
Narfström, K;Vaegan;Seeliger, M
目的：评估通过单侧rAAV介导的视网膜下基因转移治疗的一组5只RPE 65-/-犬在3年期间的视网膜结构和功能。方法：采用同步、双侧、全视野ERG进行术后功能随访。通过SLO使用FL和ICG血管造影和EM评价结构。结果：术后4周视网膜电图显示视网膜功能明显改善。暗视b波振幅在术后3个月达到峰值。然后是连续降低，尽管在所有术后时间点观察到的振幅大于基线值。A波振幅增加的时间晚于b波振幅，并在整个随访期间持续。视锥细胞功能的恢复时间比视杆细胞功能的恢复时间长。血管造影显示注射部位的结构变化，通过超微结构观察到的感光细胞破坏证实。紧邻视网膜下注射区的感光器外节表现正常。结论：尽管视网膜下注射部位局部结构改变，RPE 65无效突变犬的视网膜下基因转移在手术后至少3年内有效地增加了视网膜功能。
Aim: To assess retinal structure and function over a 3-year period in a group of five RPE65-/- dogs treated by unilateral rAAV-mediated subretinal gene transfer. Methods: Post-operative functional follow-ups were performed using simultaneous, bilateral, full-field ERGs. Structure was evaluated by SLO using FL and ICG angiography and by EM. Results: Significant improvement of retinal function was observed through ERGs approximately 4 weeks following surgery. Scotopic b-wave amplitudes peaked 3 months after surgery. Then there was a successive reduction, although greater amplitudes than base-line values were observed at all post-operative time points. A-wave amplitudes increased at a later time than b-wave amplitudes and were sustained throughout the follow-up period. The increased cone function was preserved longer than the rod function. Angiography showed structural changes at the site of injection, corroborated by photoreceptor destruction observed ultrastructurally. Immediately adjacent to the subretinal injection area photoreceptor outer segments appeared normal. Conclusion: Despite local structural alterations at the subretinal injection site, subretinal gene transfer in the RPE65 null mutation dog effectively increases retinal function for at least 3 years after surgery.