Ocular hemodynamics of rat model of glaucoma

青光眼大鼠模型眼部血流动力学

• 批准号: 9423160
• 负责人: RONALD H SILVERMAN
• 金额: $ 45.34万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9423160
• 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; Imagery; 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; Retinal; Retinal Ganglion Cells; Risk Factors; Rodent Model; Rose Bengal; Saline; Structure; System; Techniques; Technology; Time; Tissues; Ultrasonic wave; Ultrasonography; Uvea; Validation; Veins; Work; anterior chamber; aqueous; astaxanthine; base; density; experimental study; hemodynamics; improved; in vivo; intervention effect; intravenous injection; laser photocoagulation; optic nerve disorder; response; 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.

青光眼是该国和全球视力丧失不可逆转的主要原因之一。这是一个多 特征是视网膜神经节细胞（RGC）和光学的阶乘疾病或疾病家族 神经病。早就知道年龄，眼内压（IOP）和家族史是 青光眼风险因素。现在认为，减少的眼部灌注也代表了重要的危险因素。 目前，所有用于青光眼管理的医学和外科手术方法都侧重于控制IOP。可能， 校正受损的眼部灌注可能是一种富有成果的方法 管理，但要在利用此因素方面取得进展，用于评估小动物模型中流动的含义 青光眼至关重要。 我们开发了超快复合平面超声超声技术，用于可视化和测量流量 在轨道血管中，正常和青光眼的人眼的脉络膜和前部。有许多 然而，优势在将这种技术应用于青光眼的动物模型中，在那里受控的实验 可以利用条件和组织学评估。平面波提供的分辨率水平 但是，对于小型啮齿动物模型而言，技术不足。在拟议的研究中，我们将使用最近 开发了超分辨率成像（SRI）的技术来解决这一缺点。 SRI基于跟踪 对比度微泡比波长小得多，它们在微脉管系统中移动。 SRI与超快平面波成像结合使用，将用于图像轨道动脉中的血液。 在非划分限制的，次波长分辨率下，大鼠眼的脉络和前部。我们将 慢性IOP升高诱导IOP急性升高后的流动。 通过将高渗盐水注射到粘菌静脉中产生的水性流出损害，并随之而来 视神经缺血是通过视神经头部血管的激光光凝引起的。我们将确定 这些干预措施对供应眼睛，脉络膜和 前部同时。动脉和脉络膜流之间的时间段将被视为 卵巢依从性的指标，可能会改变青光眼。累积IOP和血流的度量 损伤将与RGC和视神经损伤在组织学上相关。我们还将对待 具有betaxolol的眼部高血压大鼠，以降低IOP和astaxanthin，以增强脉络膜流量，并 测量并比较它们对IOP，流量和组织损伤的影响。 拟议的研究将展示一种新技术，用于表征轨道和紫外线，使得 使用临床前模型来探索改善眼部灌注对青光眼神经病的影响。