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.

青光眼是我国乃至全世界不可逆视力丧失的主要原因之一。这是一个多- 因子性疾病，或疾病家族，特征为视网膜神经节细胞（RGC）和视神经细胞的死亡。 神经病变长期以来，人们都知道年龄、眼内压（IOP）升高和家族史是影响眼内压的重要因素。 青光眼的危险因素现在认识到，减少的眼部灌注也代表显著的风险因素。 目前，青光眼管理的所有医疗和手术方法都集中在控制IOP上。很有可能， 眼灌注受损的矫正可能是一种有效的方法， 管理，但要在利用这一因素的手段取得进展，以评估流动的小动物模型， 青光眼是至关重要的 我们开发了超快复合平面波超声技术，用于流动的可视化和测量 在正常和青光眼的眼眶血管、脉络膜和眼前节中。有很多 然而，在将该技术应用于青光眼的动物模型时， 条件和组织学评价。平面波提供的分辨率水平 然而，这种技术对于小型啮齿动物模型是不够的。在拟议的研究中，我们将使用最近的 开发了超分辨率成像（SRI）技术来解决这一缺点。SRI基于跟踪 当微泡移动通过微脉管系统时，它们比波长小得多。 SRI与超快平面波成像相结合，将用于对眼眶动脉中的血流进行成像， 在非衍射极限、亚波长分辨率下的大鼠眼脉络膜和眼前节。我们将 通过前房插管术表征急性IOP升高后的血流，通过慢性IOP升高诱导 通过将高渗盐水注射到巩膜外静脉中产生的房水流出障碍， 激光光凝视神经乳头血管引起的视神经缺血。我们将确定 这些干预对供应眼睛、脉络膜和视网膜的主要血管中的眼血流的影响 前段同时动脉和脉络膜血流之间的时间滞后将被认为是一个 葡萄膜顺应性的指标，其可在青光眼中改变。累积IOP和血流量的测量 损伤将与组织学上确定的RGC和视神经损伤相关。我们还将治疗 用倍他洛尔降低IOP的高眼压大鼠，和用虾青素增强脉络膜流动，和 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表征眼眶和葡萄膜流的新技术， 使用临床前模型探索改善的眼部灌注对青光眼性神经病变的影响。