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: 8354649
• 负责人: Lisa A Ostrin
• 金额: $ 16.53万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8354649
• 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; 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. PUBLIC HEALTH RELEVANCE: The prevalence of myopia has been increasing, and is considered epidemic in some populations. High myopia can lead to blindness, and is associated with increased risk of glaucoma. This proposal aims to describe the structural and functional ocular changes that occur in lens induced myopia and look for correlations with changes occurring in an elevated IOP model of glaucoma. Furthermore, we will investigate the hypothesis that myopic eyes are more susceptible to glaucomatous damage.

描述（由申请人提供）：Lisa Ostrin毕业于休斯顿大学视光学院，获得生理光学博士学位，主修调节生理学。在她的研究生培训期间，她对视网膜生理学产生了兴趣，这使她在约翰霍普金斯大学接受了吉斯林·达格内利的博士后培训。在那里，她使用电生理学来评估使用视网膜假体的法定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，在Christine Wildsoet博士的指导下进一步实现她的学术临床医生科学家的职业目标。近视是指来自远处物体的光线在视网膜前聚焦，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，高度近视是致盲的主要原因之一。近视的发病率一直在上升，在一些人群中被认为是一种流行病。在本研究项目中，我们将利用一种相对较新的人类近视动物模型——豚鼠来进一步表征晶状体性近视的结构和功能变化。本文描述了一组研究，旨在评估近视眼睛中青光眼的高于正常患病率反映了近视眼睛生长继发的结构和功能改变的假设。在视网膜敏感性的变化，将评估行为，使用光动力学仪器，和生理上，使用目标视网膜电图协议。先进的高分辨率体内成像技术，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