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（由申请人提供）：丽莎奥斯特林毕业于休斯顿大学视光学学院，拥有生理光学的OD和博士学位，在那里她研究了屈光生理学。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与Gislin Dagnelie进行博士后培训。在那里，她使用电生理学来评估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，以进一步实现她的学术临床医生科学家的职业目标，在克莉丝汀Wildsoet博士的指导下工作。 近视（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，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，并且在一些人群中被认为是流行病。在拟议的研究计划中，一种相对较新的人类近视动物模型豚鼠将被用于进一步表征镜片诱导的近视的结构和功能变化。该提案描述了一组旨在评估以下假设的研究：近视眼中青光眼的患病率高于正常水平反映了继发于近视眼生长的结构和功能改变。将使用视动仪器在行为上和使用靶向视网膜电图方案在生理上评估视网膜敏感度的变化。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 补充的深层视神经头筛板的超微结构研究，使用电子显微镜。 为了具体评估近视眼是否更易患青光眼，将使用前房内注射微珠（微珠闭塞模型）升高正常眼和近视眼的IOP，并评价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，并且筛板和视乳头旁巩膜经历结构变形。将如上所述评价正常眼和近视眼，并根据眼轴长度和屈光不正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导青光眼，并在相同的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。它将提供寻找结构变化的功能相关性的机会。除了对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合理的结果。 该项目将在克莉丝汀·怀尔德索特博士的指导下进行，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。三位资深视觉科学家也同意担任这项工作的顾问：1）Laura Frishman博士（休斯顿大学），视网膜电图专家，他将协助完善隔离内部视网膜通路的协议 2）Austin Roorda博士（加州大学伯克利分校），他同意提供视网膜成像和图像分析方面的指导，3）罗纳德Harwerth博士（休斯顿大学），他将提供改进实验性青光眼模型方案的建议。