Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
Sci Rep. 2016 Sep 21;6:33565. doi: 10.1038/srep33565.
Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life.
色素性视网膜炎是一种进行性视网膜营养不良，可导致不可逆转的视力损害和失明。视网膜假体目前是唯一临床可用的恢复视力的治疗方法，但恢复的视力质量仍然很差。最近，有人提出，营养不良的视网膜中存在的病理性自发性过度兴奋可能会通过降低假体反应的信噪比，对视网膜假体恢复的视力质量产生负面影响。在这里，我们研究了阻断这种过度兴奋在多大程度上可以改善光遗传学视网膜假体反应。我们记录了色素性视网膜炎小鼠模型中视网膜全层培养物中表达通道视紫红质的视网膜神经节细胞的活动。使用受临床视觉评估中使用的刺激启发的复杂刺激来评估光遗传学反应的光敏感性、对比度敏感性和空间分辨率；在所有情况下，使用缝隙连接阻滞剂甲氯芬酸阻断自发性兴奋后，光遗传学反应都得到了改善。我们的结果表明，这种方法显著提高了视网膜假体恢复的视力质量，为新的临床应用铺平了道路。此外，通过阻断自发性兴奋获得的敏感性提高可能会扩展光遗传学视网膜假体的动态范围，使其能够在较低的光强度下使用，例如日常生活中遇到的光强度。
