ADENOSINE AND RETINAL BLOOD FLOW REGULATION IN NEWBORN

我们调查的长期目标是获得 了解新生儿视网膜血流的调节，以及 开发并不断扩展能够测量血液的技术 在这个组织中流动。对于这项提案，我们将使用荧光素 视频血管造影术，现已在我们的实验室直接验证，以检查 我们的假设是嘌呤代谢物腺苷是 视网膜神经元之间的细胞间信号及其供应 微循环，调节视网膜血流量的适当变化 对氧气、灌注压和葡萄糖变化的反应 动态平衡。相当多的支持性证据支持 腺苷参与视网膜血的代谢调节 从我们实验室过去两年的研究中提供了流量 好几年了。 这里提出的用来验证我们的假设的实验将在 新生猪内源性眼压模型的建立。…的行为 视网膜腺苷将由选择性药物调节，这将是 微灌注于视网膜小动脉的开通表面 小静脉。由此产生的药理效应将表明 腺苷参与特定的流动反应；使用类似的 协议设计，我们还打算确定第二个信使调解 腺苷的血管扩张作用。从录像带记录来看，情况- 最先进的图像分析软件将允许我们在 相同的动物和选定的荧光示踪剂的速度， 动静脉传递时间，以及小动脉和小静脉直径 我们可以计算视网膜血流量。 建议的研究具有相当大的临床意义。在 新生儿，视网膜微循环调节障碍 被认为是该病高发的主要原因 继续困扰这一人群的视网膜病变。因此，它是 必须了解控制视网膜血液的生理机制 在常见的、临床上非常重要的情况下流动。只有到那时我们才能 希望制定预防或治疗的治疗策略 这些循环系统的病变。

The long-term objectives of our investigations are to gain an understanding of the regulation of retinal blood flow in the newborn, and to develop and continually expand techniques capable of measuring blood flow in this tissue. For this proposal, we will use fluorescein videoangiography, now directly validated in our laboratory, to examine our hypothesis that the purine metabolite adenosine serves as the intercellular signal between retinal neurons and their supplying microcirculation, mediating appropriate changes in retinal blood flow in response to alterations in oxygen, perfusion pressure, and glucose homeostasis. Considerable supportive evidence in favor of the involvement of adenosine in the metabolic regulation of retinal blood flow has been provided from studies in our laboratory over the last two years. Experiments proposed herein to test our hypothesis will be undertaken in a newborn pig model with endogenous intraocular pressure. The action of retinal adenosine will be modulated by selective drugs, which will be microsuffused onto the abluminal surfaces of retinal arterioles and venules. The resulting pharmacologic effect will then indicate adenosine's involvement in a particular flow response; using a similar protocol design, we also intend to identify second messengers mediating adenosine's vasodilatative effect. From the videotape record, state-of- the-art image analysis software will allow us to determine repeatedly in the same animal and velocities of selected fluorescent tracers, arteriovenous transit times, and arteriolar and venular diameters, from which we can calculate retinal blood flow. The proposed studies have considerable clinical relevance. In the newborn, disorders in the regulation of the retinal microcirculation are considered primary causative factors in the high incidence of retinopathies that continue to afflict this population. thus, it is essential to know the physiologic mechanisms controlling retinal blood flow under common, clinically-important conditions. Only then can we hope to develop therapeutic strategies for the prevention or treatment of these circulatory pathologies.