PHYSIOCHEMICAL REGULATION OF RETINAL HEMODYNAMICS

理化因素深刻地影响着人体的代谢状态 眼睛，然而大多数都是模糊的。此申请涉及调查 转化为几种可能改变视网膜和大脑的系统性因素 血流动力学，目标是首先定义正常的调节 反应，因此存在于糖尿病患者或 青光眼的特征是。 第一个具体目标是定义独立的眼睛效应 全身氧气、二氧化碳和运动水平的变化。视网膜总血流量 血流、平均视网膜毛细血管血流速度、视网膜不均质性 毛细血管流速、中央凹周围毛细血管间距离和大小 将用扫描激光测量黄斑中心凹无血管区的 检眼镜。眼压，使用Goldmann压平术 眼压测量，以及对比敏感度和视力测试， 将进一步定义眼睛的反应。颈动脉和眼动脉 使用彩色多普勒成像测量的血流量将提供第二个 明确眼血流动力学与 区域灌流。 这项拟议研究的第三个目标是确定 视网膜和区域循环调节对O2、CO2和 无视网膜病变的糖尿病患者的运动 糖尿病和眼底镜下视网膜病变的证据，年龄匹配 健康的人。第四个目标是定义血液中不同水平的 与糖尿病患者相比，年龄匹配的对照组中的葡萄糖影响 视网膜和大脑的调节反应。 正常人视网膜和脑循环调节功能的比较 青光眼将构成第五个具体目标。……的一个子群 有高眼压但没有青光眼的人将被包括在内。 低碳酸血症和适度运动都能显著降低眼压： 据推测，这些刺激物可能显著增强视网膜 眼压过高和青光眼患者的血流。最终的具体目标 是为了定义药物(一种非选择性的β-肾上腺素能阻滞剂，一种 选择性β1-肾上腺素能阻滞剂和外用碳酸氢酶 已知可降低眼压、影响视网膜、 健康眼的眼部、脑血流调节功能 年长的。 这些拟议的研究将是第一个同时调查 视网膜、眼科和脑血流调节。放置 视网膜循环在其区域背景下将促进对 糖尿病视网膜病变和青光眼的病理生理学 外用降眼压药物发挥作用的机制。 这一认识可能会加速开发新的血管活性化合物以 治疗眼科疾病。

Physiochemical factors profoundly influence the metabolic status of the eye, yet most are poorly defined. This application involves investigation into several systemic factors that may alter retinal and cerebral hemodynamics, the objective being first to define the normal regulatory response, so that regulatory dysfunctions that exist in diabetic or glaucomatous eyes can be characterized. The first specific aim is to define the independent ocular effects of variations in systemic O2, CO2, and exercise level. Total retinal blood flow, mean retinal capillary flow velocity, the inhOmogeneity of retinal capillary flow rates, the perifoveal intercapillary distance, and the size of the foveal avascular zone will be measured with a scanning laser ophthalmoscope. Intraocular pressure, using Goldmann applanation tonometry, along with testing of contrast sensitivity and visual acuity, will further define the ocular response. Carotid and ophthalmic arterial blood flow, measured using color doppler imaging, will provide the second specific aim of defining the relationship of ocular hemodynamics to regional perfusion. The third goal of the proposed research is to determine the differences in retinal and regional circulatory regulatory response to O2, CO2, and exercise among diabetic patients without retinopathy, patients with diabetes and ophthalmoscopic evidence of retinopathy, and age-matched healthy persons. A fourth aim is to define how varying levels of blood glucose, in age-matched control as compared with diabetic patients, affect retinal and cerebral regulatory responses. Retinal and cerebral circulatory regulation in healthy as compared with glaucomatous eyes will comprise the fifth specific aim. A subgroup of persons with ocular hypertension but without glaucoma will be included. Both hypocapnia and moderate exercise acutely lower intraocular pressure: it is hypothesized that these stimuli may significantly enhance retinal flow in ocular hypertensives and glaucoma patients. The final specific aim is to define how drugs (a non-selective beta-adrenergic blocker, a selective beta1-adrenergic blocker, and a topical carbonic anhydrase inhibitor) that are known to lower intraocular pressure, affect retinal, ophthalmic, and cerebral flow regulation in healthy eyes, both young and old. These proposed studies will be the first to simultaneously investigate retinal, ophthalmic, and cerebral blood flow regulation. Placing the retinal circulation in its regional context will advance understanding of the pathophysiology of diabetic retinopathy and glaucoma, and of the mechanisms by which topical ocular hypotensive drugs exert their actions. This understanding may expedite development of new vasoactive compounds to treat eye diseases.