Ocular hemodynamics of rat model of glaucoma

青光眼大鼠模型眼部血流动力学

• 批准号: 10164790
• 负责人: RONALD H SILVERMAN
• 金额: $ 43.47万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164790
• 关键词: 3-Dimensional; Acute; Address; Aftercare; Age; Algorithms; Animal Model; Anterior; Area; Arteries; Betaxolol; Blindness; Blood; Blood Circulation; Blood flow; Cannulations; Cardiac; Cessation of life; Choroid; Chronic; Country; Data; Development; Disease; Dyes; Evaluation; Eye; Family; Foundations; Glaucoma; Goals; Histologic; Hour; Human; Image; Impairment; Individual; Injections; Intervention; Ischemia; Ischemic Optic Neuropathy; Lasers; Measurement; Measures; Medical; Methods; Microbubbles; Modeling; Morphology; Neuropathy; Ocular Hypertension; Ocular orbit; Operative Surgical Procedures; Optic Disk; Optic Nerve; Optics; Oral; Perfusion; Pharmaceutical Preparations; Phase; Physiologic Intraocular Pressure; Pre-Clinical Model; Rattus; Recording of previous events; Reproducibility; Research; Resolution; Retina; Retinal Ganglion Cells; Risk Factors; Rodent Model; Rose Bengal; Saline; Structure; System; Techniques; Technology; Time; Tissues; Ultrasonic wave; Ultrasonography; Uvea; Validation; Veins; Visualization; Work; anterior chamber; aqueous; astaxanthine; base; density; experimental study; hemodynamics; improved; in vivo; intervention effect; intravenous injection; laser photocoagulation; nerve damage; optic nerve disorder; response; retinal damage; virtual

Glaucoma is one of the primary causes of irreversible vision loss in this country and worldwide. It is a multi- factorial disease, or family of diseases, characterized by death of retinal ganglion cells (RGCs) and optic neuropathy. It has long been known that age, elevated intraocular pressure (IOP) and family history are glaucoma risk factors. It is now appreciated that reduced ocular perfusion also represents a significant risk factor. At present, all medical and surgical approaches to glaucoma management focus on control of IOP. Potentially, correction of impaired ocular perfusion might be a fruitful approach in conjunction with conventional management, but to make progress in exploiting this factor means for evaluating flow in small animal models of glaucoma will be crucial. We developed ultrafast compound plane-wave ultrasound technology for visualization and measurement of flow in the orbital vessels, choroid and anterior segment of the normal and glaucomatous human eye. There are many advantages, however, in applying this technique to animal models of glaucoma, where controlled experimental conditions and histologic evaluation can be utilized. The level of resolution provided by the plane-wave technique, however, is inadequate for small rodent models. In the proposed study, we will use the recently developed technique of super-resolution imaging (SRI) to address this shortcoming. SRI is based on tracking of contrast microbubbles which are much smaller than a wavelength as they move through the microvasculature. SRI, in combination with ultrafast plane wave imaging, will be used to image blood-flow in the orbital arteries, choroid and anterior segment of the rat eye at non-diffraction limited, sub-wavelength resolution. We will characterize flow after acute elevation of IOP by anterior chamber cannulation, by chronic IOP elevation induced by impairment of aqueous outflow produced by injection of hypertonic saline into the episcleral veins, and with optic nerve ischemia induced by laser photocoagulation of vessels at the optic nerve head. We will determine the effect of these interventions on ocular blood flow in the major vessels supplying the eye, the choroid and anterior segment simultaneously. Time-lags between arterial and choroidal flow will be considered as an indicator of uveal compliance, which may be altered in glaucoma. Measures of cumulative IOP and blood flow impairment will be correlated with RGC and optic nerve damage determined histologically. We will also treat ocular hypertensive rats with betaxolol, to lower IOP, and with astaxanthin, to enhance choroidal flow, and measure and compare their effects on IOP, flow and tissue damage. The proposed research will demonstrate a new technique for characterization of orbital and uveal flow, enabling use of preclinical models for exploring the effect of improved ocular perfusion on glaucomatous neuropathy.

在这个国家和全世界，青光眼是导致不可逆转视力丧失的主要原因之一。这是一个多方面的- 以视网膜神经节细胞(RGC)和视神经细胞死亡为特征的工件性疾病或疾病家族 神经病。人们早就知道，年龄、高眼压和家族史是 青光眼危险因素。现在人们意识到，眼血流灌注减少也是一个重要的危险因素。 目前，所有治疗青光眼的内科和外科方法都集中在控制眼压上。有可能， 矫正眼血流灌注受损可能是一种卓有成效的方法，与传统的 管理，但要在利用这一因素方面取得进展，就意味着评估小动物模型中的流动 青光眼将是至关重要的。 我们开发了用于流动可视化和测量的超快复合平面波超声技术。 在正常和青光眼的眼眶血管、脉络膜和眼前段。有很多 然而，将这项技术应用于青光眼动物模型的优势，在那里控制实验 可以利用条件和组织学评估。平面波提供的分辨率水平 然而，对于小型啮齿动物模型来说，这项技术是不够的。在拟议的研究中，我们将使用最近的 针对这一缺陷，发展了超分辨率成像(SRI)技术。SRI基于对 与之形成对比的是，当微泡穿过微血管系统时，它们比波长小得多。 SRI将与超快平面波成像相结合，用于成像眼眶动脉的血液流动， 大鼠眼球的脉络膜和前段在非衍射受限的亚波长分辨率下。我们会 前房插管急性眼压升高后慢性眼压升高的血流特征 通过向巩膜上静脉注射高渗盐水而产生的房水流出障碍，以及 激光光凝视神经头血管所致视神经缺血。我们将决定 这些干预措施对眼内主要供血血管、脉络膜和眼部血流的影响。 同时做前段手术。动脉和脉络膜血流之间的时间滞后将被视为 葡萄膜顺应性的指标，在青光眼中可能会改变。累积眼压和血流量的测量 损害将与RGC和组织学确定的视神经损害相关。我们也会请你 高眼压大鼠服用倍他洛尔，降低眼压，使用虾青素，增强脉络膜血流，以及 测量并比较它们对眼压、血流和组织损伤的影响。 这项拟议的研究将展示一种表征眼眶和葡萄膜血流的新技术，使 使用临床前模型探讨改善眼血流灌注对青光眼神经病的影响。