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，获得生理光学学士和博士学位，在那里她研究了调节生理学。在研究生培训期间，她对视网膜生理学产生了兴趣，这使她在约翰·霍普金斯大学跟随吉斯林·达涅利 (Gislin Dagnelie) 接受博士后培训。在那里，她利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科学家培训计划，在 Christine Wildsoet 博士的指导下进一步实现学术临床科学家的职业目标。 近视（nearsightedness）是指远处物体的光线聚焦在视网膜前面，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，其中高度近视是失明的主要原因之一。近视的患病率一直在增加，并且在某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，来进一步表征晶状体引起的近视的结构和功能变化。该提案描述了一组研究，旨在评估以下假设：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。视网膜敏感性的变化将使用光动仪器进行行为评估，并使用目标视网膜电图方案进行生理评估。先进的高分辨率体内成像技术可评估视网膜、脉络膜和筛板细胞水平的变化，这些研究将 辅之以使用电子显微镜对深层视神经乳头筛板进行超微结构研究。 为了具体评估近视眼是否更容易患青光眼，通过前房内注射微珠（微珠闭塞模型）来升高正常眼和近视眼的眼压，并评估其对结构和功能的影响。在青光眼中，视网膜变薄，视网膜敏感性降低，筛板和乳头旁巩膜出现结构畸形。将如上所述评估正常眼和近视眼，并根据眼轴长度和屈光不正来分析青光眼损伤程度。 该项目代表了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影响的结构和功能。它将提供寻找结构变化的功能关联的机会。除了提供对这些疾病的新见解之外，预防和治疗这些疾病的新方法也是可能的结果。 该项目将在 Christine Wildsoet 博士的指导下进行，她在正视化和近视眼生长领域拥有丰富的知识，并接受过验光和药理学培训。三名资深视觉科学家也同意担任这项工作各方面的顾问：1）Laura Frishman 博士（休斯顿大学），视网膜电图专家，将协助完善隔离视网膜内部通路的方案 2) Austin Roorda 博士（加州大学伯克利分校）同意提供视网膜成像和图像分析方面的指导，3) Ronald Harwerth 博士（休斯顿大学）将为完善实验性青光眼模型的方案提供建议。 公共卫生相关性：近视的患病率一直在增加，在某些人群中被认为是流行病。高度近视可导致失明，并与青光眼风险增加相关。该提案旨在描述晶状体引起的近视中发生的结构和功能性眼部变化，并寻找与青光眼眼压升高模型中发生的变化的相关性。此外，我们将研究近视眼更容易受到青光眼损伤的假设。