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(申请人提供)：一种灵活的，基于蛋白质的，离子介导的视网膜植入物被提出用于视网膜退行性疾病患者的视力恢复，例如年龄相关性黄斑变性(AMD)和视网膜色素变性(RP)。正在开发的植入物使用含有视网膜的蛋白质--细菌视紫红质(BR)，将光转化为pH梯度。这种梯度能够激活视网膜的神经回路，特别是所有的双极细胞和神经节细胞。细菌视紫红质是一种从盐沼古生物中分离出来的光驱动质子泵，这种蛋白质的量子效率几乎与视紫红质相同，视紫红质是眼睛杆状外节中的蛋白质。BR的高热稳定性和光化学稳定性使其成为蛋白质视网膜植入物的光活性介质的极佳候选者。植入物将通过使用局部pH梯度来激活视网膜的神经电路，方法是降低剩余神经细胞周围环境的pH。正在开发的柔性植入物可以被入射光激活以产生视觉反应，并且不需要任何外部设备或电线，这是相对于竞争的基于电极的技术的优势。这一阶段研发计划中提出的实验将确定最佳蛋白质层数，以及激活50%双极细胞所需的最低光能阈值。将在切除的P23H大鼠视网膜(人类常染色体显性显性RP模型)上探索和测试植入物的视网膜下方向，以收集相对激活效率并评估时空分辨率。视网膜神经节细胞的激活将通过与波士顿退伍军人医院的Ralph Jensen博士合作的细胞外记录实验I来验证。其次，将在装置上加入一层额外的衬底，以密封植入物的周边。这第二层将用于将植入物的生物成分从眼内区域包裹起来，因此，将增强植入物的生物兼容性，降低炎症或免疫反应的风险。最后，基因工程BR将被用来产生薄膜，然后在P23H大鼠视网膜上进行体外测试。将探索由BR的状态突变体组成的薄膜，以允许操纵或消除外部像素，这将有助于选择性地调整视网膜植入物的活性区域。在这项第一阶段研究结束时，最佳的视网膜植入物设计将被确认用于随后的活体动物实验。