Gearhart Patricia M, Gearhart Chris, Thompson Debra A, Petersen-Jones Simon M
Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
Arch Ophthalmol. 2010 Nov;128(11):1442-8. doi: 10.1001/archophthalmol.2010.210. Epub 2010 Sep 13.
To determine the efficacy of intravitreal administration of 9-cis-retinal in restoring visual function in Rpe65-mutant dogs.
Intravitreal injection of 9-cis-retinal was administered in 1 eye of 7 Rpe65-/- dogs at a range of ages. Electroretinogram analysis and testing of visual performance was used to evaluate outcomes after a single injection and in 2 dogs after a second injection in the same eye.
In 5 of 7 injected dogs, 9-cis-retinal injection resulted in increased rod electroretinogram responses and improved functional vision. Three injected dogs exhibited increased 33-Hz flicker amplitudes characteristic of cone-mediated responses. Electroretinogram improvement was no longer evident by week 10 postinjection in 1 dog monitored over time. A second injection of 9-cis-retinal was performed in the same eye of 2 of the 7 dogs and also resulted in rescue of visual function.
Our findings establish that 9-cis-retinoid therapy can restore visual function in a canine model of human disease resulting from RPE65 mutations.
These positive proof-of-principle results provide support for the development of intravitreal devices for sustained delivery of 9-cis-retinal as a therapy for conditions resulting from failure of the visual cycle.
确定玻璃体内注射9-顺式视黄醛对恢复Rpe65基因突变犬视觉功能的疗效。
对7只不同年龄的Rpe65 - / - 犬的1只眼睛进行玻璃体内注射9-顺式视黄醛。单次注射后以及同一只眼睛第二次注射后，对2只犬进行视网膜电图分析和视觉性能测试以评估结果。
在7只注射犬中的5只，9-顺式视黄醛注射导致视杆细胞视网膜电图反应增加和功能性视力改善。3只注射犬表现出锥细胞介导反应特有的33赫兹闪烁幅度增加。随着时间的推移，在1只接受监测的犬中，注射后第10周视网膜电图改善不再明显。对7只犬中的2只同一只眼睛进行了第二次9-顺式视黄醛注射，也导致了视觉功能的恢复。
我们的研究结果表明，9-顺式视黄酸疗法可以在由RPE65突变引起的人类疾病犬模型中恢复视觉功能。
这些积极的原理验证结果为开发用于持续递送9-顺式视黄醛的玻璃体内装置提供了支持，作为治疗视觉循环失败导致的病症的一种疗法。
