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/F028539/1
• 负责人: Mark Hankins
• 金额: $ 44.17万
• 依托单位: University of Oxford
• 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%2FF028539%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色素性视网膜炎 (RP)，影响视杆细胞和视锥细胞感光细胞，是发达国家第二大失明原因。这些病症的特征可能是外视网膜中主要光敏细胞的灾难性损失。最常见的是视杆细胞营养不良，最初会出现周边视力丧失，随后中央视力下降，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）正迅速成为最常见的失明形式。 AMD 中央视力受到影响，现在是西方世界 60 岁以上最常见的失明原因。据预测，随着人口老龄化和AMD的流行，将会出现严重的医疗危机。 RP、AMD 和 DR 患者通常都保留正常的视神经和视网膜神经节细胞，这些细胞形成视神经/视觉皮层的通讯高速公路。这些特征提出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，这种策略避免了与修复退化视网膜组织相关的复杂性。迄今为止，该领域的尝试有两种形式：试图刺激退化视网膜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前植入物。虽然在这些领域，甚至最近的临床试验中取得了一些进展，但该技术仍有四个实质性问题尚未完全解决：1) 手术进入和生物相容性2) 从物理假体到 RGC 的信息传输的长期效率，导致高刺激电流要求 3) 与使用当前技术可用的极低电极密度相关的空间分辨率的缺乏 4) 当前技术无法恢复近黄斑 由于缺乏视神经盘附近的传入神经节细胞体的视网膜专题图，因此无法实现功能的所有这些问题中，最严重的是每个电极刺激神经节细胞所需的能量消耗。所需电流可能高达 2mA，这意味着重建图像所需的大型像素阵列将需要不可行的能量。最近的一项进展发现，一小部分 RGC（<0.1%）本身对光直接敏感，这为视力恢复技术的新范例开辟了可能性。他们通过采用一种与视杆细胞和视锥细胞视蛋白完全不同的新型视蛋白感光色素，克服了 RGC 中的光检测问题。这些感光 RGC 的功能似乎是调节与时间相关的光响应（例如昼夜节律夹带），而不是生成视觉图像。最近，其他视蛋白系统也取得了进展，例如通道视紫红质和纳米颗粒光刺激。Mark Hankins 一直在神经元细胞系中表达和表征黑视蛋白。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。这与我们在智能成像芯片开发和视网膜算法开发方面的经验相结合，为我们提供了开发全新类别视网膜假体的绝佳机会。基于光刺激的假体可以是外部的，不会受到电刺激的功率问题，并且易于调整和升级。使用光将智能视网膜处理系统与幸存的视网膜神经节细胞耦合代表了视网膜假体领域的重要且显着的范式转变。