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

视网膜假体：一种恢复功能性视力的新型光电仿生方法。

• 批准号: EP/F029241/1
• 负责人: Patrick Degenaar
• 金额: $ 44.47万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF029241%2F1
• 关键词: Retinal; prosthetics; novel; opto; bionic

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.

遗传性退行性疾病，统称为视网膜色素变性(RP)，影响视杆和视锥感光细胞，是发达国家第二大致盲原因。这些情况的特征可能是外层视网膜中初级感光细胞的灾难性丧失。最常见的是视杆-视锥细胞营养不良，最初是周边视力丧失，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)和糖尿病视网膜病变(DR)正迅速成为最常见的失明形式。在老年性黄斑变性中，中心视力受到影响，现在是西方世界60岁以上的人最常见的致盲原因，S。据预测，随着人口老龄化和AMD的流行，将会出现一场重大的医疗危机。RP、AMD和DR患者通常都保留了正常的视觉器官和视网膜神经节细胞，这些细胞构成了视神经/通往视觉皮质的通信高速公路。这些特点增加了临床假体干预可以绕过病变组织并刺激剩余健康细胞的可能性，一种避免与修复该地区退化的视网膜组织相关的复杂性的策略迄今已有两种形式：试图刺激变性视网膜的剩余神经处理层的视网膜下植入物，以及试图直接刺激视网膜神经节细胞层的视网膜外植入物。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，但这项技术仍有四个实质性问题尚未完全解决：1)手术通路和生物相容性2)信息从物理假体传输到视网膜节细胞的长期效率，导致高刺激电流要求3)缺乏空间分辨率，与现有技术提供的极低密度电极相关4)现有技术无法接近黄斑附近功能的恢复，因为缺乏对视盘附近传入神经节细胞体的视网膜原位标测其中最严重的是刺激神经节细胞所需的每个电极的能量消耗。所需电流可能高达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。最近的一项发展为视力恢复技术开辟了一种新的范式，它发现了一小部分RGC(&lt；0.1%)本身直接对光敏感。他们使用了一种与杆状和锥状光学元件截然不同的新型光学元件，从而克服了RGC中的光探测问题。这些感光RGC的功能似乎是调节一天中依赖于时间的光反应，如昼夜节律携带，而不是产生视觉图像。最近，在其他视素系统方面也有了进展，如通道罗波辛和纳米颗粒光刺激。马克·汉金斯一直在神经细胞系中表达和表征黑素。此外，Patrick Degenaar一直在研究不涉及基因工程的纳米颗粒刺激的替代方法。这一点，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，给了我们一个很好的机会来开发一种全新的视网膜假体。基于光刺激的假体可以是外部的，不受电刺激的电力问题，并且易于调整和升级。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着视网膜假体领域重要而重大的范式转变。