SBIR Phase II: Design and Optimization of a Biocompatible Protein-Based Retinal Implant for the Treatment of End-Stage Retinal Degeneration

这个小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力是开发一种基于蛋白质的高分辨率视网膜植入物并将其商业化，旨在为数百万因视网膜退行性疾病(尤其是视网膜色素变性和老年性黄斑变性)而失明的患者恢复视力。这些目前无法治愈的致盲疾病影响着全世界3000万至5000万人，并导致个人丧失独立性，并增加了照顾者的负担。虽然提高生活质量是这项技术最重要的成果，但降低治疗慢性视网膜变性的医疗成本和限制与医生见面的时间也将有利于广泛的医疗领域。SBIR提案中概述的工作也有可能显著影响我们对视网膜退行性疾病的理解，这将有助于为许多眼科适应症开发更好、更有效的治疗方法。正在开发的视网膜下植入物为下一代高分辨率视网膜假体提供了框架，同时为视力恢复提供了一种经济高效的解决方案，并将帮助这些患者重新获得独立，从而提高他们的生活质量。拟议的项目将扩大从我们的I/IB阶段奖项支持的体内外科开发和体外疗效研究中收集的数据。首先，将进行一项40只动物的大鼠研究，以进一步调查视网膜植入物的生物相容性。其次，之前开发的手术程序将在猪身上进行改进，以确保视网膜下植入的可重复性和安全性。第三，将设计一种高通量的体外测试来研究植入物的一些参数，以及使用视网膜色素上皮细胞的视网膜植入物的完整性和生物稳定性。此外，医疗器械密封剂将在这项体外研究中进行研究，并将使用时间分辨吸收光谱和专门为此应用开发的离子敏感检测器来测量植入物的功能完整性。最后，这种离子敏感探测器将提供一个机会，进一步测量高分辨率的视网膜植入物的空间敏感性。这些体内和体外研究对于继续评估植入物的生物相容性、手术可行性和有效性至关重要。这些研究的结果将进一步证明正在开发的技术的商业可行性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop and commercialize a high resolution, protein-based retinal implant intended to restore vision to the millions of patients blinded by retinal degenerative diseases, particularly retinitis pigmentosa and age-related macular degeneration. These currently incurable and blinding diseases affect between 30-50 million people worldwide, and lead to a loss of independence for the individual, as well as an increased burden on their caregivers. While improved quality of life is the most vital outcome of this technology, reduction of medical costs of treating chronic retinal degeneration and limiting time with doctors will also be of benefit to the broad healthcare field. The work outlined in this SBIR proposal also has the potential to significantly impact our understanding of retinal degenerative diseases, which will help in developing better and more effective treatments for a number of ophthalmic indications. The subretinal implant under development provides the framework for the next generation of high-resolution retinal prosthetics, while offering a cost-effective solution to vision restoration, and will help these patients regain independence and thus improve their quality of life. The proposed project will expand on the data collected from the in vivo surgical development and ex vivo efficacy studies supported by our Phase I/IB awards. First, a 40-animal rat study will be undertaken to further investigate the biocompatibility of the retinal implant. Second, previously developed surgical procedures will be refined in pigs to ensure reproducible and safe subretinal implantation. Third, a high-throughput in vitro assay will be designed to investigate a number of implant parameters, as well as the integrity and biostability of the retinal implant using retinal pigment epithelial cells. Additionally, medical device sealants will be investigated in this in vitro study, and the functional integrity of the implant will be measured using time-resolved absorption spectroscopy and an ion-sensitive detector, which is being developed specifically for this application. Lastly, this ion-sensitive detector will provide an opportunity to further measure the spatial sensitivity of the retinal implant with high resolution. These in vivo and in vitro studies are vital for the continued evaluation of biocompatibility, surgical feasibility, and efficacy of the implant. The results from these studies will further demonstrate the commercial viability of the technology under development.