Flexible Ion-Mediated Artificial Retina

柔性离子介导人工视网膜

• 批准号: 8710818
• 负责人: ROBERT Richards BIRGE
• 金额: $ 19.05万
• 依托单位: LAMBDAVISION, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8710818
• 关键词: Action Potentials; Adhesives; Age related macular degeneration; Animal Experiments; Animals; Archaea; Architecture; Area; Bacteriorhodopsins; Biocompatible; Biocompatible Materials; Biological; Blinded; Boston; Calibration; Cells; Collaborations; Development; Development Plans; Devices; Electrodes; Electrophysiology (science); Encapsulated; Evaluation; Eye; Film; Genetic Engineering; Goals; Hospitals; Human; Immune response; Implant; Inflammation; Inflammatory; Ions; Light; Mediating; Mediation; Medical Device; Methods; Modeling; Neurons; Optics; Patients; Phase; Photoreceptors; Polymers; Preparation; Procedures; Process; Production; Property; Proteins; Proton Pump; Rattus; Relative (related person); Reproducibility; Resolution; Retina; Retinal; Retinal Degeneration; Retinal Ganglion Cells; Retinitis Pigmentosa; Rhodopsin; Risk; Rod Outer Segments; Running; Silicones; Sodium Chloride; Spatial Distribution; Sterilization; Surface; System; Techniques; Technology; Testing; Time; Vision; Visual; base; biomaterial compatibility; dacron; density; design; extracellular; flexibility; ganglion cell; human tissue; implantation; improved functioning; in vivo; light intensity; mutant; neural circuit; pH gradient; phase 1 study; polycation; prototype; public health relevance; quantum; research and development; research study; response; restoration; retinal stimulation; seal; spatiotemporal

DESCRIPTION (provided by applicant): A flexible, protein-based, ion-mediated retinal implant is proposed for the restoration of vision for patients with retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). The implant under development uses the retinal- containing protein, bacteriorhodopsin (BR), to convert light into a pH gradient. This gradient is capable of activating the neural circuitry of the retina, specificall the bipolar and ganglion cells. Bacteriorhodopsin is a light-driven proton pump isolated from a salt-marsh archaeon and this protein has a quantum efficiency nearly identical to rhodopsin, the protein in the rod outer segments of the eye. The high thermal and photochemical stability of BR make it an excellent candidate for use as the photoactive medium in a protein-based retinal implant. The implant will operate by using a local pH gradient to activate the neural circuitry of the retina by decreasing the pH in the milieu surrounding the remaining neural cells. The flexible implant under development can be activated by incident light to generate a visual response and will not require any external apparatus or wires, an advantage over competing electrode-based technologies. The experiments proposed in this Phase I research and development plan will determine the optimal number of protein layers, in addition to the lowest threshold of light energy required to activate 50% of bipolar cells. A subretinal orientation of the implant will be explored and tested on excised P23H rat retinas (model of human form of autosomal dominant RP) to collect relative activation efficiencies and evaluate spatiotemporal resolution. Activation of retinal ganglion cells will be verified through the use of extracellular recording experiments i collaboration with Dr. Ralph Jensen at the Boston VA Hospital. Secondly, an additional layer of substrate will be incorporated onto the device to seal the perimeter of the implant. This second layer will be used to encapsulate the biological components of the implant from the intraocular domain, and as a result, will enhance the biocompatibility of the implant and reduce the risk of inflammation or an immune response. Lastly, genetically engineered BR will be used to generate thin films that will then be tested on P23H rat retinas ex vivo. Thin films consisting of state mutants of BR will be explored to allow for the manipulation or elimination of extraneous pixels, which will facilitate selective tuning of the active area of the retinal implant. At the conclusion of this Phase I study, the best retinal implant design will be confirmed for use in subsequent in vivo animal experiments.

描述（由申请人提供）：提出了一种基于蛋白质的，基于蛋白质的离子介导的视网膜植入物，用于恢复视觉退行性疾病患者的视力，例如与年龄相关的黄斑变性（AMD）和视网膜炎色素炎（RP）。发育中的植入物使用含有视网膜的蛋白质细菌紫红素（BR）将光转化为pH梯度。该梯度能够激活视网膜的神经回路，特异性双极和神经节细胞。细菌紫红蛋白是一种从盐沼库中分离的轻驱动质子泵，该蛋白的量子效率几乎与视紫红蛋白相同，Rhodopsin是眼睛的棒外部片段中的蛋白质。 BR的高热和光化学稳定性使其成为基于蛋白质的视网膜植入物中光活性培养基的绝佳候选者。该植入物将通过使用局部pH梯度来激活视网膜的神经回路，从而通过减少剩余神经细胞的环境中的pH值来激活视网膜的神经回路。可以通过入射光激活正在开发的柔性植入物以产生视觉响应，并且不需要任何外部设备或电线，这比基于竞争的电极技术的优势是优势。 除激活50％的双极细胞所需的最低光能阈值外，在本I阶段研究和开发计划中提出的实验还将确定蛋白质层的最佳数量。将在切除的P23H大鼠视网膜（常染色体显性RP的人类形式模型）上探索和测试植入物的视网膜下取向，以收集相对活化效率并评估时空分辨率。通过使用细胞外记录实验I与波士顿VA医院的Ralph Jensen博士合作，将验证视网膜神经节细胞的激活。其次，将在设备上合并一层底物以密封植入物的周围。该第二层将用于封装从眼内结构域中植入物的生物学成分，结果将增强植入物的生物相容性并降低炎症或免疫反应的风险。最后，基因工程的BR将用于生成薄膜，然后将在P23H大鼠视网膜上进行测试。将探索由BR状态突变体组成的薄膜，以允许操纵或消除外部像素，这将促进视网膜植入物的活性区域的选择性调整。在本阶段研究的结论结束时，将确认最好的视网膜植入物设计用于随后的体内动物实验。