SBIR Phase I: Development of a Protein-Based Retinal Implant

这项小型企业创新研究（SBIR）I期项目的更广泛影响/商业潜力是开发和商业化一种高分辨率、基于蛋白质的视网膜植入物，旨在恢复数百万患有视网膜退行性疾病（特别是视网膜色素变性和年龄相关性黄斑变性）的患者的视力。这些目前无法治愈的致盲性疾病影响着全世界3000万至5000万人，并导致个人失去独立性，并增加了其护理人员的负担。此外，除了视力丧失的情感和身体负担外，仅在美国，视力问题的成本估计为1390亿美元。SBIR提案中概述的工作有可能显著影响我们对视网膜退行性疾病以及视网膜修复领域的理解。正在开发的视网膜下植入物为下一代高分辨率视网膜修复提供了框架，同时为视力恢复提供了具有成本效益的解决方案，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。 --该项目旨在量化一种灵活的、基于蛋白质的、离子介导的视网膜植入物的空间分辨率，并对该植入物进行体内初步评估。正在开发的视网膜植入物是第一种使用光激活蛋白质细菌视紫红质将光能转化为离子梯度的植入技术，该离子梯度能够激活退化视网膜的剩余神经回路。视网膜植入物将取代受损感光细胞的功能。将使用从视网膜色素变性转基因大鼠模型获得的切除视网膜离体评价空间分辨率。将进行细胞外微电极阵列实验，以证明植入物的分辨率，这对有意义的视觉至关重要。将通过对家猪进行6周可行性研究，在体内评价植入物的安全性和有效性。这些体内研究对于确定植入物的外科手术以及生物相容性和生物稳定性至关重要，为植入物的长期、严格、临床前有效性试验（作为II期研究的一部分）做准备。这些实验是关键的价值创造里程碑，将证明正在开发的视网膜植入物的商业可行性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop and commercialize a high resolution, protein-based retinal implant intended to restore vision to the millions of patients suffering from 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. Additionally besides the emotional and physical burden of vision loss, the cost of vision problems in the US alone is estimated at $139 billion. The work outlined in this SBIR proposal has the potential to significantly impact our understanding of retinal degenerative diseases, as well as the field of retinal prosthetics. 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 seeks to quantify the spatial resolution of a flexible, protein-based, ion-mediated retinal implant, as well as to perform an initial evaluation of the implant in vivo. The retinal implant under development is the first implantable technology to use the light-activated protein, bacteriorhodopsin, to convert light energy into an ion gradient that is capable of activating the remaining neural circuitry of the degenerate retina. The retinal implant will replace the function of the damaged photoreceptor cells. Spatial resolution will be evaluated ex vivo using excised retinas obtained from a transgenic rat model of retinitis pigmentosa. Extracellular microelectrode array experiments will be carried out to demonstrate the resolution of the implant, which is critical for meaningful vision. Safety and efficacy of the implant will be evaluated in vivo via a 6-week feasibility study on domestic swine. These in vivo studies are critical to establish the surgical procedures and biocompatibility and biostability of the implant in preparation for long-term, rigorous, preclinical efficacy testing of the implant as part of Phase II investigations. These experiments are critical value creation milestones that will demonstrate the commercial viability of the retinal implant under development.