Structural and Functional Characterization of a Novel Model for Glaucoma Research

描述(由申请人提供)：该项目的基本目标是建立一种用于人类青光眼研究的棚屋、自发、遗传的猫科动物模型。一个可行的繁殖群体已经建立，我们已经确定这种形式的猫科青光眼是作为常染色体隐性遗传特征遗传的。这项建议概述了一个五年计划，在这个猫科动物的家系中对原发性青光眼进行严格的临床、功能和形态特征描述。在该项目的头三年，将通过非侵入性手段(包括眼压测量、高分辨率超声、荧光光度测量、光学相干断层扫描和电生理学)以及视网膜和视神经病理的组织形态评估对一组猫进行纵向评估，以表征疾病进展的自然历史并建立结构功能相关性。在该项目的最后几年，我们将开始检查降低眼压作为一种神经保护性治疗策略在进一步的猫队列中对疾病进展的结果。拟议的研究结果将为青光眼复杂的病理生理基础提供线索。 并将阐述NEI青光眼和视神经疾病研究计划的一些关键研究重点。这项提案的候选人是一名在比较眼科领域接受过临床和博士培训的兽医。这项研究项目将为培训计划提供一个框架，在各自领域的领先研究人员的指导下，这将使应聘者有机会获得新的实验室研究技能，以及在道德、负责任和有效开展研究方面的进一步培训。拟议的培训计划将为候选人提供青光眼研究方面的强大背景，并为其作为学术兽医临床医生和独立研究人员的职业生涯奠定基础。青光眼是人类失明的一个重要原因。目前，由于缺乏可获得的、特征良好的大型动物模型，青光眼患者有效治疗策略的开发受到阻碍。一旦确定了特征，这种模式将为其他研究人员提供宝贵的资源，并将促进将实验室研究结果转化为新的临床战略，以便及早发现和更有效地治疗人类患者的这种致残性疾病。

DESCRIPTION (provided by applicant): The fundamental goal of this project is to establish a hovel, spontaneous, inherited feline model for human glaucoma research. A viable breeding colony has been established and we have determined that this form of feline glaucoma is inherited as an autosomal recessive trait. This proposal outlines a five-year plan to conduct rigorous clinical, functional and morphological characterization of primary glaucoma within this pedigree of cats. Over the first 3 years of the project, a cohort of cats will be evaluated longitudinally by both non-invasive means (including tonometry, high resolution ultrasonography, fluorophotometry, optical coherence tomography and electrophysiology) and by histomorphological evaluation of retinal and optic nerve pathology, in order to characterize the natural history of disease progression and establish structure function correlations. In the final years of the project we will begin to examine the outcomes of intraocular pressure-lowering as a neuroprotective treatment strategy on disease progression in a further cohort of cats. Results of the proposed studies will provide clues as to the complex patho-physiological basis of glaucoma and will address a number of key research priorities of the NEI's research program in glaucoma and optic neuropathies. The candidate of this proposal is a veterinarian with prior clinical and PhD training in the field of comparative ophthalmology. This research project will provide a framework for a training program, under the mentorship of leading researchers in their respective fields, which will afford the candidate the opportunity to gain new laboratory research skills as well as further training in the ethical, responsible and efficient conduct of research. The proposed training program will provide the candidate with a strong background in glaucoma research and serve as the foundation for a career as an academic veterinary clinician and independent researcher. Glaucoma is an important cause of vision loss in the human population. The development of effective treatment strategies for glaucoma patients is currently hampered by a lack of accessible, well-characterized, large animal models. Once characterized, this model will represent a valuable resource for other investigators and will facilitate the translation of laboratory research findings into new clinical strategies for the early detection and more effective treatment of this disabling disease in human patients.