System for Ocular Oxygen Measurements

描述（由申请人提供）：本项目的目的是开发用于测量眼睛上和眼睛内氧气浓度的系统。这些系统将利用对氧浓度敏感的磷光探针。它们将在眼科研究中有明显的应用，并将导致我们对眼科疾病的理解，新药开发，隐形眼镜和外科手术的进步。应该强调的是，这些仪器系统仅针对眼科研究市场，而不是临床诊断市场。我们相信，这一市场对此类产品的需求很大，而且它们的使用将对我们理解眼睛中的氧气、其在眼部疾病中的作用以及新药、隐形眼镜、其他治疗器械和外科手术的开发产生重大影响。我们最初的技术使用了一个双频光子计数系统，这是我们专门为此目的而开发的。它结合了最高的灵敏度和测量宽范围氧浓度的能力。在第一阶段，我们证明了我们的技术在体外和兔眼中的可行性。这些研究表明，我们可以使用更灵活的可编程光子计数系统，该系统可以跨越宽范围的频率，从而允许使用宽范围的磷光探针。自本申请的最后一次修订以来，我们已经实施了这一新设计，并使用体外溶液和活兔对其进行了测试。有一个广泛的磷光染料，我们建议他们中的许多人的能力，渗透或不渗透到不同的眼组织的特点。磷光猝灭不限于氧。在第一阶段中使用的染料系统先前已被证明是相对不敏感的其他眼睛变量，但任何新的染料也将有类似的特点。包括人类在内的许多动物系统已被用于以前的眼氧研究。我们打算利用Ocuplant开发的三个交付平台来访问全系列的动物系统：人类，实验室动物（灵长类动物，兔子等），和非常小的实验室动物（小鼠）。我们的总体目标是开发基于染料的多个测量系统，这些染料已被选择用于特定的环境亲和力、氧气范围等。一个关键目标是标准化和校准控制，以便在不同的机器上获得的结果具有可比性。此外，我们将设计具有足够灵活性的仪器，以便我们可以随着新的磷光氧探针和技术的开发而增加功能。 与公共卫生的关系：氧气是生命的基础，但它的存在不仅赋予生命，其反应性也可能导致功能障碍。拟议的仪器将利用对氧浓度敏感的磷光探针来监测眼睛各个区域的氧浓度。这将在眼科研究、药物和隐形透镜测试中有明显的应用。

DESCRIPTION (provided by applicant): The purpose of this project is to develop systems for measuring oxygen concentrations on and inside the eye. These systems will take advantage of phosphorescent probes that are sensitive to oxygen concentrations. They will have obvious applications in eye research and will lead to advancements in our understanding of ocular diseases, development of new drugs, contact lenses and surgical procedures. It should be emphasized that these instrument systems are aimed solely at the ophthalmic research market, and NOT at the clinical diagnostic market. We believe that there is both a significant demand for such products in this market, and that their use will have significant impact to our understanding of oxygen in the eye, its role in ocular disease, and the development of new drugs, contact lenses, other therapeutic devices, and surgical procedures. Our initial technique used a dual frequency photon counting system, which we developed specifically for this purpose. It combined maximum sensitivity with the ability to measure a wide range of oxygen concentrations. During Phase I, we demonstrated feasibility of our techniques both in vitro and in the rabbit eye. These studies indicated that we could use a more flexible programmable photon counting system that could span a wide range of frequencies allowing the use of a wide range of phosphorescent probes. Since the last revision of this application, we have implemented this new design and tested it with both in vitro solutions and with live rabbits. There are a wide range of phosphorescent dyes available, and we propose to characterize many of them for their ability to penetrate or not penetrate into different ocular tissue. Phosphorescence quenching is not limited to oxygen. The dye system used in Phase I has previously been shown to be relatively insensitive to other ocular variables, but any new dyes will also have to be characterized similarly. A number of animal systems including humans have been used in previous research on ocular oxygen. We intend to leverage three delivery platforms developed by OcuMetrics to access the full range of animal systems: humans, laboratory animals (primates, rabbits, etc.), and very small laboratory animals (mice). Our overall goal is to develop multiple measurement systems based on dyes that have been selected for specific environmental affinity, oxygen range, etc. A critical goal will be standardization and calibration control, so that results made on different machines will be comparable. In addition, we will design this instrument with enough flexibility so that we can add capabilities as new phosphorescent oxygen probes and techniques are developed. PUBLIC HEALTH RELEVANCE: Oxygen is fundamental to life, but its presence is not only life giving, its reactive nature can also lead to dysfunction. The proposed instrument will take advantage of phosphorescent probes that are sensitive to oxygen concentrations to monitor oxygen concentrations in various areas of the eye. This will have obvious applications in eye research, and drug and contact lens testing.