Retinal prosthetics: a novel opto-bionic approach to the restoration of functional vision.

遗传性退行性疾病，统称为视网膜色素变性（RP），影响视杆细胞和视锥细胞，是发达国家第二大致盲原因。这些病症的特征可以是外层视网膜中的初级光敏细胞的灾难性损失。最常见的是视杆-视锥营养不良，最初是周边视力丧失，随后是中心视力衰退，导致完全失明。视网膜相关性黄斑变性（AMD）和糖尿病视网膜病变（DR）正在迅速成为最普遍的失明形式。在AMD中，中央视力受到影响，并且它现在是西方世界60年代最常见的致盲原因。据预测，随着人口老龄化和AMD的流行，将出现重大的医疗保健危机。RP、AMD和DR的患者通常都保留正常的视器官和形成视神经/到视觉皮层的通信高速公路的视网膜神经节细胞的存活群体。这些特征提高了临床假体干预可以绕过患病组织并刺激剩余健康细胞的可能性，这是一种避免与修复退化视网膜组织相关的复杂性的策略。视网膜下植入物试图刺激退行性视网膜的剩余神经处理层，以及试图直接刺激视网膜神经节细胞层的视网膜前植入物。虽然在这些领域取得了一些进展，最近甚至进行了临床试验，但这项技术还没有完全解决四个实质性问题：1）手术通路和生物相容性2）从物理假体到RGC的信息传递的长期效率，导致高刺激电流要求3）与使用当前技术可用的极低密度的电极相关的空间分辨率的缺乏4）当前技术不能接近近黄斑功能的恢复，由于缺乏视神经盘附近的传入神经节细胞体的视网膜定位图。在所有这些问题中，最严重的是每个电极刺激神经节细胞所需的能量功耗。所需的电流可以高达2 mA，这意味着重建图像所需的大像素阵列将需要不可行的能量。最近的一项发展开启了视力恢复技术新范式的可能性，即发现一小部分RGC（<0.1%）本身直接对光敏感。他们通过采用与视杆和视锥视蛋白完全不同的新型视蛋白色素来克服RGC中的光检测问题。这些光感受性RGC的功能似乎是调节一天中的时间依赖性光反应，如昼夜节律的夹带，而不是产生视觉图像。最近，在其他视蛋白系统如通道rhodposin和纳米颗粒光刺激方面也有了进展。Mark Hankins一直在神经元细胞系中表达和表征黑视蛋白。此外，帕特里克Degenaar一直在研究替代方法的纳米粒子刺激，不涉及基因工程。结合我们在智能成像芯片和视网膜算法开发方面的经验，这为我们提供了开发全新视网膜假体的绝佳机会。基于光刺激的假体可以是外部的，不受电刺激的功率问题的影响，并且容易调整和升级。使用光将智能视网膜处理系统耦合到存活的视网膜神经节细胞代表了视网膜假体领域的重要和显著的范式转变。

Hereditary degenerative diseases, collectively classed as retinitis pigmentosa (RP) affect the rod and cone photoreceptors and are the second largest cause of blindness in the developed world. These conditions may be characterised by a catastrophic loss of the primary light sensitive cells in the outer retina. Most common are rod-cone dystrophies, where there is initially a loss of peripheral vision followed by a decay of central vision leading to total blindness. Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are fast becoming the most prevalent forms of blindness. In AMD central vision is affected, and it is now the commonest cause of blindness in the western world in the over 60's. It is predicted that there will be a significant healthcare crisis as the population is ageing and AMD is prevalent. Sufferers of RP, AMD and DR generally all retain a normal optic apparatus and a viable population of retina ganglion cells that form the optic nerve / the communication superhighway to the visual cortex. These features raise the possibility that clinical prosthetic intervention could bypass the diseased tissue and stimulate the remaining healthy cells, a strategy that avoids the complexities associated with repairing the degenerate retinal tissue Attempts to date in this area have come in two forms: subretinal implants which attempt to stimulate the remaining neural processing layers of the degenerative retina, and epiretinal implants which have attempted to stimulate the retinal ganglion cell layer directly. While there is some progress in these areas, and recently even clinical trials, there are four substantial problems that this technology has yet to fully address:1) Surgical access and biocompatibility2) Long-term efficiency of information transfer from the physical prosthesis to the RGCs, leading to high stimulation current requirements3) The lack of spatial resolution associated with the very low density of electrodes available using current technology4) The inability of the current technologies to approach restoration of near macular function, because of the lack of retinotopic mapping of the afferent ganglion cell bodies in the vicinity of the optic diskOf all these issues the most serious is the energy power consumption required per electrode to stimulate ganglion cells. Required currents can be as high as 2mA meaning that the large pixel arrays required for recreating images would require unfeasible quantities of energy. A recent development that opens the possibility of a new paradigm in vision restoration technology has been the discovery that a small percentage of RGCs (<0.1%) are themselves directly light sensitive. They overcome the problems of light detection in RGCs by employing a novel opsin photopigment that is quite different from rod and cone opsins. The function of these photoreceptive RGCs appears to be the regulation of time-of-day dependent photoresponses such as circadian entrainment rather than generating visual images. More recently there have also been developments in other opsin systems such as channel rhodposin and nanoparticle light stimulation.Mark Hankins has been expressing and characterising melanopsin in neuronal cell lines. In addition Patrick Degenaar has been investigating alternate methods of nanoparticle stimulation which does not involve genetic engineering. This, combined with our experience in the development of intelligent imaging chips and retinal algorithm development, gives us a great opportunity to develop a whole new class of retinal prosthesis. A photostimulation-based prosthesis can be external, not suffer the power problems of electrical stimulation, and be easily tuned and upgraded.Using light to couple an intelligent retinal processing system to the surviving retinal ganglion cells represents an important and significant paradigm shift in field of retinal prosthetics.