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具有不同的潜在病理生理，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、病灶激光和手术，要么不能解决视网膜缺氧问题，要么以损害视网膜组织为代价。此外，即使在大约50%的患者中玻璃体内注射抗血管内皮生长因子或激光，视力也没有改善。我们的跨学科团队的生物学家，物理学家，工程师和医生从七个机构已经采取了一种新的方法来治疗缺血性视网膜疾病。在本提案中，利用复杂的生物实验，生物信息学，生物物理学和先进的生物微机电系统（bioMEMS）工程，我们提出了一个OXYGENATOR系统，以提供高度控制的氧气水平，精确地针对缺血视网膜（即治疗窗口内的局部氧合）。我们在无线生物电子植入物（OXYGENATOR）的工程方面取得了重大进展，它可以以可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（单一符合人体工程学，灵活，低轮廓设计，适用于白天和晚上使用）提供感应（RF）链接

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.