A Novel Treatment for Retinal Ischemia

描述（由申请人提供）：糖尿病视网膜病变（DR）和视网膜静脉阻塞（RVO）是低视力和失明的主要原因。 虽然DR和RVO具有不同的基础病理生理学，但继发于缺血的视网膜内缺氧是这些疾病的核心。 现有的治疗方法，如药物注射、全视网膜光凝、聚焦激光和手术，要么不能解决视网膜缺氧问题，要么以损伤视网膜组织为代价。 此外，即使玻璃体内注射抗血管内皮生长因子或激光，在大约50%的患者中，视力也没有改善。 我们来自七个机构的生物学家，物理学家，工程师和医生的跨学科团队已经采取了治疗缺血性视网膜疾病的新方法。 在该提案中，使用复杂的生物实验、生物信息学、生物物理学和先进的生物微机电系统（bioMEMS）工程，我们提出了一种OXYGENATOR系统，以提供精确靶向缺血视网膜的高度受控水平的氧气（即，治疗窗内的局部氧合）。 我们已经在无线生物电子植入物（OXYGENATOR）的工程方面取得了重大进展，该植入物可以以受控的方式向视网膜输送安全量的氧气。 氧合器由两个单元组成;一个可穿戴，另一个可植入。 眼外可穿戴组件（单一人体工程学、灵活、低剖面设计，适用于白天和夜间使用）提供感应（RF）链路 电力和数据。 可植入组件包括用于接收电力和数据的电子器件、连接到透氧膜袋内的MEMS电极以进行电解的电子电路以及用于补充透氧膜袋内的盐水的可再填充盐水储存器。 包 当外部组件在定制软件控制下向植入式电子设备传输功率和数据时，氧合器运行（注：软件可根据每位患者的需求进行个性化设置）。 植入的电子器件接收、解码并向MEMS电极递送受控的电脉冲，以导致氧气可渗透膜袋内的盐水的电解。 然后，氧气以受控和定向的方式扩散出袋到达视网膜，同时屏蔽诸如透镜的前眼结构。 虽然在数月的电解过程中仅使用纳升的盐水，但设计了可再填充的盐水储液器，用于补充渗透袋内的盐水，以将氧合器的使用寿命延长至5年以上。 在这份提案中，我们分享了我们迄今为止在这种新方法上的成果，并概述了我们在3个具体目标方面的研究计划。 在临床前研究中成功完成这三个目标将使我们能够吸引后续的工业资金来开展临床研究。 第一个目标是使用短期和长期测试来量化细胞和组织水平上的视网膜氧需求。 第二个目标是设计氧合器，以证明长期功效并最大限度地提高效率。 第三个目标是研究氧气的生产和扩散的时空动态控制电解在眼睛。

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR) and retinal vein occlusions (RVO) are major causes of low vision and blindness. Although DR and RVO have different underlying pathophysiology, inner retinal hypoxia secondary to ischemia is central to these diseases. Existing therapeutic approaches like pharmacological injections, pan-retinal photocoagulation, focal laser, and surgery either do not address retinal hypoxia or do so at the cost of damaging retinal tissue. Moreover, even with intravitreal injections of anti-Vascular Endothelial Growth Factors, or laser, in approximately 50% of patients, vision does not improve. Our interdisciplinary team of biologists, physicists, engineers, and physicians from seven institutions has taken a novel approach towards treating ischemic retinal disease. In this proposal, using sophisticated biological experiments, bioinformatics, biophysics and advanced bio-microelectromechanical systems (bioMEMS) engineering, we propose an OXYGENATOR system to deliver highly controlled levels of oxygen that are precisely targeted to the ischemic retina (i.e., local oxygenation within a therapeutic window). We have made significant advances towards engineering of a wireless bioelectronic implant (OXYGENATOR) that can deliver safe amounts of oxygen to the retina in a controlled manner. The OXYGENATOR consists of two units; one wearable and the other implantable. The extraocular wearable components (single ergonomic, flexible, low profile design for day and night time use) provide the inductive (RF) link for power and data. The implantable components consist of electronics to receive power and data, electronic circuitry attached to MEMS electrodes inside oxygen permeable membrane bag for electrolysis, and a refillable saline reservoir to replenish the saline inside oxygen permeable bag. The OXYGENATOR functions when the external component transmits power and data under customized software control to the implanted electronics (note software can be personalized for each patient need). The implanted electronics receive, decode and deliver controlled electrical pulses to the MEMS electrodes to result in electrolysis of the saline inside the oxygen permeable membrane bag. The oxygen then diffuses in a controlled and directional manner out the bag to the retina while shielding the anterior eye structures such as the lens. Although only nanoliters of saline are used over months of electrolysis, a refillable saline reservoir to replenish the saline inside the permeable bag has been designed to lengthen the life of the OXYGENATOR to 5+ years. In this proposal, we share our results to date on this novel approach and outline our research program in 3 specific aims. Successful completion of these 3 aims in preclinical studies will enable us to attract follow-on industrial funding to embar on clinical studies. The first aim is to use short and long term tests to quantify the retinal oxyen requirements at the cellular and tissue level. The second aim is to engineer the OXYGENATOR to demonstrate long-term efficacy and maximize efficiency. The third aim is to study the spatiotemporal dynamics of oxygen production and diffusion by controlled electrolysis in the eye.