A Novel Treatment for Retinal Ischemia

视网膜缺血的新疗法

基本信息

批准号：
8926993
负责人：
MARK S HUMAYUN
金额：
$ 82.74万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8926993
关键词：
Address Adverse effects Animal Model Anterior Biochemistry Bioinformatics Biological Biophysics Blindness Canis familiaris Central Scotomas Characteristics Cicatrix Clinical Research Computer software Consumption Dark Adaptation Data Devices Diabetic Retinopathy Diffuse Diffusion Disease Electrodes Electrolyses Electronics Engineering Experimental Models Eye Functional disorder Funding Genetic Recombination Goals Health Histology Hybrids Hyphema Hypoxia Immunohistochemistry Implant Injection of therapeutic agent Institution Iris Ischemia Knowledge Laser Surgery Lasers Letters Life Light Coagulation Link Location Low-Level Laser Therapy Measurement Membrane Metabolism Modeling Oryctolagus cuniculus Outcome Oxygen Patients Performance Peripheral Pharmaceutical Preparations Physicians Physiologic Intraocular Pressure Physiologic pulse Physiology Process Production Publications Research Retina Retinal Retinal Diseases Retinal Vein Occlusion Risk Saline Secondary to Structure System Technology Testing Theoretical model Therapeutic Time Tissues Toxic effect Vascular Diseases Vascular Endothelial Growth Factors Vascular Permeabilities Vision Visual Acuity Visual Fields Visual impairment Vitrectomy Wireless Technology Work cost design diabetic electronic data ergonomics flexibility improved in vivo intravitreal injection laser photocoagulation lens macular edema metabolic abnormality assessment nano nanolitre neovascularization novel novel strategies operation oxidative damage preclinical study prevent programs ranibizumab research study retinal damage retinal ischemia spatiotemporal standard of care time use treatment duration

项目摘要

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.

描述（由申请人提供）：糖尿病性视网膜病（DR）和视网膜静脉阻塞（RVO）是低视力和失明的主要原因。尽管DR和RVO具有不同的潜在病理生理学，但缺血继发的视网膜缺氧是这些疾病的核心。现有的治疗方法，例如药理学注射，泛视网膜光凝，焦点激光和手术，要么不解决视网膜缺氧或以损害视网膜组织的代价来解决。此外，即使玻璃体内注射抗血管内皮生长因子或激光，大约50％的患者也不会改善视力。我们来自七个机构的生物学家，物理学家，工程师和医师的跨学科团队采取了一种新颖的方法来治疗缺血性视网膜疾病。在该建议中，使用复杂的生物学实验，生物信息学，生物物理学和先进的生物微电机力学系统（BioMems）工程，我们建议使用一种氧合系统来提供高度控制的氧气，这些氧气含量高度控制于缺血性视网膜（即，在局部氧气内）（即，在局部氧气内（均具有更高的氧气）。我们已经在工程化无线生物植入物（氧合剂）方面取得了重大进步，该植入物可以以受控的方式向视网膜提供安全量的氧气。氧合剂由两个单位组成；一个可穿戴，另一个可植入。眼外可穿戴组件（单人体工程学，柔性，日夜时间的低调设计）提供感应性（RF）链接用于电源和数据。可植入的组件由电子设备组成，以接收电力和数据，可用于电解的氧气渗透膜袋内的MEMS电极，以及可再填充的盐水储层，以补充可渗透氧气内的盐水包。当外部组件将定制软件控制下的功率和数据传输到植入的电子设备时（可以为每个患者需要个性化注意软件）时，充氧剂的功能。植入的电子设备接收，解码并传递受控的电脉冲到MEMS电极，从而导致氧气渗透膜袋内的盐水电解。然后，氧气以受控和方向的方式扩散到视网膜上，同时遮盖镜头等前眼结构。尽管仅在数月的电解中使用了盐水的纳米含量，但已经设计了可再填充的盐水来补充可渗透袋中的盐水，以使氧合寿命延长至5年以上。在此提案中，我们在这种新颖的方法上分享了迄今为止的结果，并以3个特定目标概述了我们的研究计划。临床前研究中这三个目标的成功完成将使我们能够吸引随后的工业资金来违反临床研究。第一个目的是使用短期和长期测试来量化细胞和组织水平的视网膜氧需求。第二个目的是设计氧合剂以证明长期疗效并最大化效率。第三个目的是研究氧气产生的时空动力学和通过受控的电解在眼中的传播。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Spatial Variations in Vitreous Oxygen Consumption.

DOI：
10.1371/journal.pone.0149961
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Murali K;Kang D;Nazari H;Scianmarello N;Cadenas E;Tai YC;Kashani A;Humayun M
通讯作者：
Humayun M

Whole vitreous humor dissection for vitreodynamic analysis.