Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ, 07103, USA.
Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, 90 Bergen Street, Newark, NJ, 07103, USA.
Sci Rep. 2021 Jan 12;11(1):692. doi: 10.1038/s41598-020-80267-4.
Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1-2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.
视网膜脱离 (RD) 会导致 rod 光感受器-双极突触的分离损伤，从而破坏视力，并可能导致视网膜再附着手术后观察到的视力恢复不佳。我们在成年雌性猪中创建了一种医源性 RD 模型，以研究损伤后 rod-bipolar 突触的损伤以及高度特异性 Rho 激酶 (ROCK) 抑制剂保留突触结构和功能的能力。该模型模拟了人类在将病毒载体或细胞注入视网膜下以治疗视网膜疾病时使用的程序。通过共聚焦切片的图像分析定量 rod 小体的回缩，在脱离后 2 小时即可观察到突触分离，并持续存在 2 天，尽管此时视网膜已经自发再附着。此外，在与脱离视网膜 1-2cm 的附着视网膜中也观察到了小体回缩。无论通过视网膜下注射还是玻璃体内注射，ROCK 抑制均可显著减少脱离视网膜中的突触损伤。在再附着的视网膜中记录暗适应全视野视网膜电图，以评估 rod 特异性功能。突触损伤的减少与药物治疗眼的 rod 驱动反应增加相关。因此，ROCK 抑制有助于防止视网膜损伤后的突触损伤，并改善功能结果，可能是医源性 RD 和其他视网膜变性疾病的有用辅助治疗方法。
