Feasibility study of electrically evoked multifocal ERG in end-stage RP

描述（由申请人提供）：这个高风险，高回报项目的直接目标是开发一种非侵入性的评估方法，在电子视网膜假体接受者的视网膜电活动。在过去几年中，这些用于终末期视网膜变性失明患者的视网膜植入物的开发和临床评价取得了相当大的进展，至少有六个国家的研究小组和公司正在积极进行。然而，了解变性视网膜中由电刺激引起的生理反应仍然是难以捉摸的，并且迫切需要揭示其机制。已知人RP中缓慢的视网膜变性过程从根本上改变了剩余的视网膜双极细胞、无长突细胞和神经节细胞之间的相互作用;因此，使用动物模型对理解失明植入物接受者视网膜中的活性几乎没有帮助。因此，非侵入性的方法来评估这一活动的发展将是对理解和改善这些患者报告的视觉感觉的主要贡献。该建议建立在多焦临床电生理学技术的基础上，该技术在过去二十年中发展并广泛用于视网膜和视觉通路病理学的诊断，以研究由视网膜植入物接受者中植入电极的均匀和图案化刺激产生的视网膜信号。基于二进制m序列的植入电极的伪随机开关刺激将引起局部视网膜响应和二阶相互作用，其将通过完善的互相关技术从单个角膜记录信号中提取。初步证据表明，电刺激伪影可以有效地减少，以揭示视网膜反应活动，但需要相当大的努力来完善这种方法，以克服不利的信号伪影比，适应刺激和分析技术，优化刺激方法，估计直接响应信号和相互作用的强度，并开发相关的生理和心理物理反应的方法。拟议项目期限为两年。 公共卫生相关性：为了阐明视网膜变性（如视网膜色素变性）致盲患者的视网膜电刺激过程中发生的过程，将开发一种非侵入性刺激和记录方法。这种技术对于解释最近引入的视网膜植入物的临床结果以及推进功能性视网膜假体的发展至关重要。

DESCRIPTION (provided by applicant): The immediate goal of this high-risk, high-payoff project is to develop a non-invasive assessment methodology of electrical activity in the retina of electronic retinal prosthesis recipients. The development and clinical evaluation of these retinal implants for patients blind from end-stage retinal degenerations has made considerable progress in the last several years and is being actively pursued by research groups and companies in at least a half dozen countries. Understanding the physiological response elicited by the electrical stimulus in the degenerated retina remains elusive, however, and there is an urgent need to uncover its mechanisms. It is known that the slow retinal degeneration process in human RP fundamentally alters the interactions between remaining retinal bipolar, amacrine, and ganglion cells; hence the use of animal models is of little help in understanding the activity in the retina of a blind implant recipient. Thus the development of noninvasive methods to assess this activity would be a major contribution towards understanding and improving the visual sensations reported by these patients. This proposal builds on multifocal clinical electrophysiology techniques, developed in the last two decades and widely used for diagnosis of retinal and visual pathway pathology, to investigate the retinal signals generated by uniform and patterned stimulation of implanted electrodes in retinal implant recipients. Pseudo-random on-off stimulation of the implanted electrodes, based on binary m-sequences, will elicit localized retinal responses and second-order interactions that will be extracted from a single corneal recording signal through well-established cross correlation techniques. Preliminary evidence suggests that the electrical stimulus artifact can be effectively reduced to reveal the retinal response activity, but a considerable effort is needed to perfect this approach to overcome the adverse signal to artifact ratio, adapt the stimulation and analysis techniques, optimize stimulation methods, estimate the strength of direct response signals and interactions, and develop ways to correlate physiological and psychophysical responses. A two-year project duration is proposed. PUBLIC HEALTH RELEVANCE: To elucidate the processes that take place during electrical stimulation of the retina in patients blind from retinal degenerations such as retinitis pigmentosa, a noninvasive stimulation and recording methodology will be developed. Such a technique is crucial for the interpretation of clinical findings with recently introduced retinal implants, and to advance the development of functional retinal prostheses.