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

遗传性退行性疾病，统称为色素性视网膜炎（RP），影响杆状和锥状光感受器，是发达国家致盲的第二大原因。这些病症的特征可能是外层视网膜主要感光细胞的灾难性损失。最常见的是杆状锥体营养不良症，最初是周围视力丧失，然后是中心视力衰退，导致完全失明。年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变（DR）正迅速成为最普遍的失明形式。在AMD中，中枢视力受到影响，它现在是西方世界60多岁人群失明的最常见原因。据预测，随着人口老龄化和AMD的普遍存在，将会出现重大的医疗危机。RP、AMD和DR患者通常都保留了正常的视觉器官和可存活的视网膜神经节细胞群，这些细胞形成了视神经/与视觉皮层的通信高速公路。这些特征提高了临床假体干预绕过病变组织并刺激剩余健康细胞的可能性，这种策略避免了修复退化视网膜组织的复杂性。迄今为止，在这一领域的尝试有两种形式：视网膜下植入物试图刺激退化视网膜的剩余神经处理层，视网膜外植入物试图直接刺激视网膜神经节细胞层。虽然在这些领域取得了一些进展，最近甚至有临床试验，但这项技术还没有完全解决四个重大问题：1)手术准入和生物相容性；2)从物理假体到RGCs的信息传输的长期效率；导致高刺激电流需求3)缺乏空间分辨率，与使用现有技术的电极密度非常低有关4)由于缺乏视盘附近传入神经节细胞体的视网膜定位，目前的技术无法接近恢复近黄斑功能。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率消耗。所需电流可高达2毫安，这意味着再现图像所需的大像素阵列将需要不可行的大量能量。最近的一项研究发现，一小部分RGCs（<0.1%）本身是直接光敏的，这为视觉恢复技术的新范式开辟了可能性。他们通过使用一种与杆状视蛋白和锥状视蛋白完全不同的新型视蛋白光色素，克服了RGCs中光检测的问题。这些感光rgc的功能似乎是调节依赖于时间的光反应，如昼夜节律干扰，而不是产生视觉图像。最近也有其他视蛋白系统的发展，如通道rhodposin和纳米粒子光刺激。马克·汉金斯一直在神经细胞系中表达和表征黑视素。此外，Patrick Degenaar一直在研究不涉及基因工程的纳米粒子刺激的替代方法。结合我们在智能成像芯片开发和视网膜算法开发方面的经验，这给了我们一个很好的机会来开发一种全新的视网膜假体。基于光刺激的假肢可以是外部的，不受电刺激的电力问题的困扰，并且很容易调整和升级。利用光将智能视网膜处理系统与存活的视网膜神经节细胞耦合是视网膜修复领域的一个重要而重要的范式转变。

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.