Structural and Functional Characterization of a Novel Model for Glaucoma Research

项目描述（申请人提供）：本项目的基本目标是建立一个用于人类青光眼研究的猫的自发遗传模型。一个可行的繁殖群体已经建立，我们已经确定，这种形式的猫青光眼是遗传为常染色体隐性性状。该提案概述了一个五年计划，以进行严格的临床，功能和形态学特性的原发性青光眼在这个谱系的猫。在项目的前3年，将通过非侵入性方法（包括眼压测量、高分辨率超声检查、荧光光度测定、光学相干断层扫描和电生理学）以及视网膜和视神经病理学的组织形态学评价对一组猫进行纵向评价，以表征疾病进展的自然史并建立结构功能相关性。在该项目的最后几年，我们将开始在另一组猫中检查降低眼内压作为疾病进展的神经保护治疗策略的结局。这些研究结果将为青光眼复杂的病理生理基础提供线索 并将解决NEI在青光眼和视神经病变研究计划中的一些关键研究优先事项。该提案的候选人是一名兽医，具有比较眼科学领域的临床和博士培训。该研究项目将提供一个培训计划的框架，在各自领域的领先研究人员的指导下，这将使候选人有机会获得新的实验室研究技能，以及在道德，负责任和有效的研究行为方面的进一步培训。拟议的培训计划将为候选人提供强大的青光眼研究背景，并作为学术兽医临床医生和独立研究人员的职业基础。青光眼是人类视力丧失的重要原因。青光眼患者有效治疗策略的开发目前受到缺乏可获得的、良好表征的大型动物模型的阻碍。一旦表征，该模型将为其他研究者提供宝贵的资源，并将促进实验室研究结果转化为新的临床策略，以早期检测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.