Restoring vision in mouse models of retinal degeneration using human rod opsin.

视网膜退化是导致失明的常见原因。在许多情况下，这种退化主要是视杆和视锥感光器的一个特征，使眼睛和大脑(视神经)之间的通信通道完好无损。在有这种情况的患者中，视网膜仍然存在，但缺乏对光的反应能力。如果能恢复这些人视网膜的光敏性，就有望重建视力。这确实已经在一些使用电子假体的患者身上实现了。这将重点放在确定在退化的视网膜中再生视觉反应的最佳可能方式上。有许多令人兴奋的技术正在开发中，以实现这一目标。很可能每种方法都有各自的优点和局限性，不同的患者群体会从不同的方法中受益。因此，我们正处于一个阶段，在临床前研究中，我们需要探索各种策略来恢复退化视网膜的光敏性。最近，我们试验了一种非常简单的方法来解决这个问题--在一个失明小鼠模型的视网膜中，引入一种蛋白质，使人的视杆细胞对存活的神经元产生光感受(视杆蛋白)。我们发现，视杆蛋白可以使这些神经元具有感光能力，而且接受治疗的小鼠能够识别标准计算机显示器呈现的图案和自然电影。如果类似情况的人类患者也能获得类似的结果，我们有望让目前完全失明的患者识别一些物体，并在普通室内照明下利用视觉进行空间导航。由于这种干预包括将一种天然的人类蛋白质引入人体的一部分，这种蛋白质通常使用已经在临床上使用的方法表达，因此在人体上进行试验的安全和伦理障碍被降至最低。然而，在转移到患者身上之前，我们需要更好地了解这种新疗法是如何起作用的。在这里，我们建议在小鼠身上进行一系列实验，告诉我们这种潜在的令人兴奋的新疗法是多么安全和有效。

Degeneration of the retina is a common cause of blindness. In many cases, this degeneration is predominantly a feature of the rod and cone photoreceptors, leaving the channel of communication between the eye and brain (the optic nerve) intact. In patients with such conditions then, the retina is still present but lacks the ability to respond to light. If one could restore photosensitivity to the retina of these people, one could hope to recreate vision. This indeed has been achieved in some patients using electronic prostheses. This places the emphasis on identifying the best possible way of regenerating visual responses in the degenerate retina. There are a number of exciting technologies in development to achieve this goal. It is likely that each will have strengths and limitations and that different patient groups benefit from different approaches. We are therefore at a stage at which we need to explore a variety of strategies for restoring photosensitivity to the degenerate retina in pre-clinical studies. We recently, trialled a very simple approach to this problem - introducing the protein that makes human rods photoreceptive (rod opsin) to surviving neurones in the retina of a mouse model of blindness. We found that rod opsin could make these neurones photoreceptive, and that the treated mice were able to recognise patterns and natural movies presented with standard computer monitors. If similar results were achieved in human patients with similar conditions, we could hope to allow patients currently completely blind to recognise some objects and use vision for spatial navigation in ordinary indoor lighting. As the intervention involves introducing a native human protein into the part of the body it is ordinarily expressed using methods already in clinical use, safety and ethical barriers to trialling in humans are minimised. However, before moving to patients we need a better appreciation of how this new therapy could work. Here we propose a series of experiments in mice that will tell us how safe and effective this potentially exciting new therapy could be.