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对电子视网膜假体接受者的视网膜电活动进行非侵入性评估的方法。这些视网膜植入物的开发和临床评估在过去几年中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研究这些视网膜植入物。然而，了解电刺激在退化的视网膜中引发的生理反应仍然是难以捉摸的，迫切需要揭示其机制。众所周知，人类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，使用动物模型对了解盲目植入受者视网膜的活动几乎没有帮助。因此，开发非侵入性方法来评估这种活动将对了解和改善这些患者报告的视觉感觉做出重大贡献。这项建议建立在多焦点临床电生理技术的基础上，该技术是近20年来发展起来的，广泛用于视网膜和视觉通路病理的诊断，以研究视网膜植入受者对植入电极进行均匀和图案化刺激所产生的视网膜信号。基于二进制m序列对植入电极的伪随机开关刺激将引起局部视网膜反应和二阶相互作用，这些反应和二阶相互作用将通过成熟的互相关技术从单个角膜记录信号中提取出来。初步证据表明，电刺激伪影可以有效地减少以揭示视网膜的反应活动，但需要相当大的努力来完善这一方法，以克服不利的信噪比，适应刺激和分析技术，优化刺激方法，估计直接反应信号和相互作用的强度，并发展出将生理和心理物理反应关联起来的方法。建议项目期限为两年。 公共卫生相关性：为了阐明视网膜色素变性等视网膜变性致盲患者在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。这种技术对于解释新近推出的视网膜植入物的临床结果以及推动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.