EFRI-BSBA: Nanoactuation and Sensing of Neural Function for Engineering Future Biomimetic Retinal Implants and Therapies

PI: Laxman Saggere，机械与工业工程，伊利诺伊大学芝加哥分校（UIC）智力优势视网膜退行性疾病，如年龄相关性黄斑变性（AMD），仅在美国就影响了超过1000万人，导致他们的生活质量显著下降。目前可用的治疗方法充其量只是有些效果。在过去的二十年里，世界各地的几个小组一直在追求视网膜假体的发展，其目标是为因光感受器变性而受视网膜疾病影响的患者提供恢复援助。目前几乎所有视网膜假体的发展都依赖于电刺激视网膜的原理，这在概念上很简单；然而，在这种方法中仍有许多挑战需要克服，而且功能齐全、持久耐用的设备不会马上出现。另一方面，在正常运作的视网膜以及神经系统的其他地方，细胞间通讯的一个广泛发生的机制是化学突触。受大自然通过化学突触将视觉信息转化为化学信号的复杂机制的启发，申请人设想了一种非常规但合理的方法来恢复光感受器失去的功能：视网膜上的光调制化学界面。为了实现以化学为基础的视网膜植入物的长期愿景，拟议的项目旨在了解视网膜和视网膜神经元如何在体外对化学刺激的可控焦点表现做出生理反应，以便进一步探索基于病变神经元功能开发假肢系统的一般工程框架。有两类截然不同的化学物质，即天然神经递质和栓系合成生物分子，它们都有可能作为递质，而且每一种都有其独特的优势。因此，在这个项目中，他们建议研究通过特殊设计的微纳米级传递装置，在两种化学物质的局部刺激下，引发视网膜神经元生理反应的有效性和可行性。这种新方法从根本上不同于更常见的电刺激视网膜神经元的方法，也不同于其他小组最近提出的基于化学的策略。因此，这一提议的主要智力价值在于产生新的科学和技术知识，这些知识可能对仿生视网膜植入物的发展产生变革，以恢复失去或受损的视网膜功能。最终，如果成功，这项研究可能会导致视网膜假体的新范式和突破。这项计划如果成功，可能会在视觉假体领域开辟新天地，并有一天帮助数百万患有视网膜退行性疾病的人获得视觉知觉。与视力丧失相关的破坏性并发症，以及美国人口的逐渐老龄化，在其他健康个体中AMD的发病率相应增加，强调了国家迫切需要开发有效的视网膜退行性疾病假体和治疗方法。除了对视力健康的影响之外，这项研究还可能导致其他新的药物输送策略和用于治疗各种神经系统疾病（如帕金森病）的仿生疗法。在这个项目中，具有不同专业知识的研究人员的跨学科合作为工程、神经科学和医学前沿的中学博士后提供了跨学科教育和培训的独特机会和框架。四名研究生和一名博士后将在UIC三个不同学院的研究人员实验室进行跨学科研究，解决该项目涉及的任务。将实施若干与拟议研究相结合的教育活动，包括本科生研究和外联活动。

ABSTRACT for EFRI-BSBA: Nanoactuation and Sensing of Neural Function for Engineering Future Biomimetic Retinal Implants and Therapies PI: Laxman Saggere, Mechanical and Industrial Engineering, University of Illinois at Chicago (UIC) Intellectual Merit Retinal degenerative diseases such as age-related macular degeneration (AMD) affect over 10 million people in the US alone, causing a significant decline in the quality of their lives. Currently available therapies are at best only somewhat effective. Over the last two decades, several groups around the world have been pursuing the development of a retinal prosthesis, with the goal of providing a restorative aid for patients affected by retinal diseases due to photoreceptor degeneration. Nearly all of the current retinal prosthesis developments rely on the principle of stimulating the retina electrically, which is conceptually simple; however, a number of challenges still remain to be overcome in this approach and fully functional, long-lasting devices are not on the immediate horizon. On the other hand, a widely occurring mechanism of intercellular communication in the normally functioning retina as well as elsewhere in the nervous system is the chemical synapse. Inspired by the nature's complex mechanism of transducing visual information into chemical signals via the chemical synapse, the applicants envision an unconventional, but rational, approach to restore the lost functionality of photoreceptors: a light modulated chemical interface at the retina. Toward this long-term vision of a chemically based retinal implant, the proposed project seeks to understand how the retina and retinal neurons respond physiologically to controlled focal presentation of chemical stimuli in vitro so that a general engineering framework for developing a prosthetic system based on the functionality of the diseased neurons can be further explored. There exist two distinct classes of chemicals, viz. native neurotransmitters and tethered synthetic biomolecules, that are promising as transmitters, and each offers certain unique advantages. Therefore, in this project, they propose to investigate the efficacy and feasibility of eliciting physiological responses of retinal neurons when focally stimulated by both types of chemicals delivered by means of specially engineered micro- and nanoscale delivery devices. This novel approach is fundamentally different from the more common approach of electrically stimulating retinal neurons, and distinct from chemical-based strategies recently proposed by other groups. Thus, the main intellectual merit of this proposal lies in generating new scientific and technical knowledge that could be transformative to the development of a biomimetic retinal implant to restore lost or damaged retinal function. Ultimately, if successful, this research could lead to a new paradigm and breakthroughs in retinal prostheses. Broader Impacts The proposed project, if successful, could break new ground in the area of visual prosthesis and someday help provide vision perception to millions of people affected by retinal degenerative diseases. The devastating complications associated with vision loss, and the progressive aging of the US population with a corresponding increased incidence of AMD in otherwise healthy individuals, emphasize an urgent national need to develop effective prostheses and therapies for retinal degenerative diseases. Beyond the impact on vision health, this research could also lead to other novel drug delivery strategies and biomimetic therapies for treating a variety of neurological disorders such as Parkinson's. The interdisciplinary collaboration of researchers with a diverse expertise in this project provides a unique opportunity and framework for interdisciplinary education and training of secondary school through postdoctoral students at the frontiers of engineering, neuroscience, and medicine. Four graduate students and one postdoctoral student will undertake interdisciplinary research addressing the tasks involved in this project in the investigators' labs across three different colleges at UIC. Several educational activities integrated with the proposed research including undergraduate research and outreach will be implemented.