Structural and Functional Changes in Myopia and Susceptibility to Glaucoma

近视的结构和功能变化以及青光眼易感性

• 批准号: 8735152
• 负责人: Lisa A Ostrin
• 金额: $ 16.53万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735152
• 关键词: Affect; Animal Model; Behavioral; Birth; Blindness; Cataract; Cavia; Cessation of life; Chickens; Choroid; Collagen; Collagen Fibril; Complement; Contrast Sensitivity; Data; Deformity; Development; Disease; Distant; Doctor of Philosophy; Electron Microscopy; Electrophysiology (science); Electroretinography; Epidemic; Evaluation; Eye; Glaucoma; Goals; Growth; Health; Human; Image; Image Analysis; Imaging Techniques; In Vitro; Injection of therapeutic agent; Knowledge; Lead; Length; Life; Light; Macular degeneration; Measurement; Mentorship; Microspheres; Modeling; Mus; Myopia; Nature; Nerve; Optic Disk; Optics; Optometry; Outcome; Pathway interactions; Patients; Pattern; Pharmacology; Physiological; Physiology; Population; Predisposition; Prevalence; Prevention; Primary Open Angle Glaucoma; Primates; Process; Protocols documentation; Refractive Errors; Research; Research Design; Resolution; Retina; Retinal; Retinal Detachment; Risk; Scientist; Sclera; Secondary to; Stratification; Structure; Testing; Tissues; Training; Training Programs; Universities; Vision; Visual system structure; Work; austin; career; cell type; college; density; emmetropization; ganglion cell; in vivo; in vivo imaging; insight; instrument; interest; legally blind; lens; nonhuman primate; novel strategies; novel therapeutics; post-doctoral training; prevent; programs; retinal prosthesis; socioeconomics; vision development

DESCRIPTION (provided by applicant): Lisa Ostrin graduated from the University of Houston College of Optometry with an OD and PhD in physiological optics, where she studied accommodative physiology. During her graduate training, she became interested in retinal physiology, which led her to post-doctoral training with Gislin Dagnelie at Johns Hopkins University. There, she used electrophysiology to evaluate retinal changes in legally blind patients with retinal prostheses, after which she joined the UC Berkeley Clinician Scientist Training Program to further her career goal of an academic clinician scientist, working under the mentorship of Dr. Christine Wildsoet. Myopia (nearsightedness) refers to the condition in which light rays from distant objects come to focus in front of the retina, resulting in blurred retinal images. Myopia is associated with retinal detachment, macular degeneration, cataract and glaucoma, with high myopia being one of the leading causes of blindness. The prevalence of myopia has been increasing, and is considered epidemic in some populations. In the proposed research program, a relatively new animal model of human myopia, the guinea pig, will be used to further characterize the structural and functional changes in lens-induced myopia. This proposal describes a set of studies designed to evaluate the hypothesis that the higher than normal prevalence of glaucoma in myopic eyes reflects alteration in structure and function secondary to myopic eye growth. Changes in retinal sensitivity, will be assessed both behaviorally, using an optokinetic instrument, and physiologically, using targeted electroretinogram protocols. Advanced high resolution in vivo imaging techniques to evaluate changes at the cellular level in the retina, choroid and lamina cribrosa, and these studies will be complemented by ultrastructural studies of the lamina cribrosa of the deep optic nerve head, using electron microscopy. To specifically assess whether myopic eyes are more susceptible to glaucoma, IOP will be elevated in normal and myopic eyes using intracameral injections of microbeads (the Microbead Occlusion Model), and its effects on structure and function evaluated. In glaucoma, the retina thins, retinal sensitivity is reduced, and the lamina cribrosa and parapapillary sclera undergoes structural deformity. Normal and myopic eyes will be evaluated as described above, and the degree of glaucomatous damage will be analyzed in terms of axial length and refractive error. This project represents the first attempt to induce glaucoma in a myopic animal model and to evaluate in the same eyes, both structures and functions known to be affected in these two disease processes. It will provide opportunity to look for functional correlates of structural changes. Apart from providing new insights into these conditions, new approaches to their prevention and treatment are plausible outcomes. This project will be conducted under the mentorship of Dr. Christine Wildsoet who has extensive knowledge in the field of emmetropization and myopic eye growth, with training in Optometry and pharmacology. Three senior vision scientists have also agreed to serve as consultants on aspects of this work: 1) Dr. Laura Frishman (Univ. Houston), an expert in the electroretinography, who will assist in refining protocols for isolating the inner retinal pathways of the guinea pig, 2) Dr. Austin Roorda (Univ. Cal. Berkeley), who has agreed to give guidance on retinal imaging and image analysis, and 3) Dr. Ronald Harwerth (Univ. Houston), who will provide advice in refining the protocol for the experimental glaucoma model.

描述(申请人提供)：Lisa Ostrin毕业于休斯顿大学验光学院，获得生理光学外科学和博士学位，在那里她学习调节生理学。在研究生培训期间，她对视网膜生理学产生了兴趣，这导致她在约翰·霍普金斯大学与吉斯林·达格内利一起接受博士后培训。在那里，她使用电生理学来评估接受视网膜假体的合法失明患者的视网膜变化，之后她加入了加州大学伯克利分校临床医生科学家培训计划，以进一步实现她的职业目标，即在Christine Wildsoet博士的指导下工作，成为一名学术临床医生科学家。近视(近视)是指从远处物体发出的光线聚焦到视网膜前面，导致视网膜图像模糊的情况。近视与视网膜脱离、黄斑变性、白内障和青光眼有关，高度近视是导致失明的主要原因之一。近视的患病率一直在增加，在一些人群中被认为是流行病。在拟议的研究计划中，将使用一种相对较新的人类近视动物模型-豚鼠，进一步表征晶状体诱导近视的结构和功能变化。这项建议描述了一系列旨在评估以下假设的研究：近视眼青光眼患病率高于正常水平反映了近视眼生长继发的结构和功能的改变。视网膜敏感度的变化，将使用视动仪器进行行为评估，并使用靶向视网膜电信号方案进行生理评估。先进的高分辨率活体成像技术，以评估视网膜、脉络膜和筛板细胞水平的变化，这些研究将是 此外，还使用电子显微镜对深部视神经头部的筛板进行了超微结构研究。为了具体评估近视眼是否更容易患青光眼，将采用微珠房内注射(微珠阻塞模型)升高正常和近视眼的眼压，并评估其对结构和功能的影响。在青光眼中，视网膜变薄，视网膜敏感度降低，筛板和视乳头旁巩膜发生结构性畸形。正常眼和近视眼将如上所述进行评估，青光眼损害程度将根据眼轴长度和屈光不正进行分析。该项目首次尝试在近视动物模型中诱发青光眼，并在同一只眼睛中评估已知在这两种疾病过程中受到影响的结构和功能。它将提供寻找结构性变化的功能相关性的机会。除了为这些疾病提供新的见解外，预防和治疗这些疾病的新方法也是看似合理的结果。该项目将在Christine Wildsoet博士的指导下进行，Christine Wildsoet博士在正视和近视眼睛生长领域拥有广泛的知识，并接受过验光和药理学方面的培训。三位资深视觉科学家还同意担任这项工作各方面的顾问：1)Laura Frishman博士(大学。视网膜电描记术专家，他将协助完善隔离视网膜内通路的方案 2)Austin Roorda博士(大学卡尔。他同意在视网膜成像和图像分析方面提供指导，以及3)罗纳德·哈沃斯博士(Univ.他将在完善实验性青光眼模型的方案方面提供建议。