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）：丽莎·奥斯特林（Lisa Ostrin）毕业于休斯顿大学验光学院，并在生理光学上获得了OD和博士学位，在那里她学习了适应性生理学。在研究生培训期间，她对视网膜生理学感兴趣，这使她在约翰·霍普金斯大学的吉斯林·达格尼（Gislin Dagnelie）接受了博士后培训。在那里，她使用电生理学评估了视网膜假体合法盲人患者的视网膜变化，此后，她加入了加州大学伯克利分校的临床科学家培训计划，以进一步在学术临床科学家的职业目标中，并在克里斯汀·怀尔德索特（Christine Wildsoet）的指导下工作。 近视（近视）是指远处物体的光线聚焦在视网膜前的状况，从而导致视网膜图像模糊。近视与视网膜脱离，黄斑变性，白内障和青光眼有关，高近视是失明的主要原因之一。近视的患病率一直在增加，在某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，豚鼠将用于进一步表征镜头引起的近视的结构和功能变化。该提案描述了一系列研究，旨在评估以下假设：近视眼中青光眼的患病率高于正常患病率，反映了结构和功能的改变，其次是近视眼的生长。视网膜敏感性的变化将使用靶向的电视图方案，并在生理上进行行为评估。先进的高分辨率体内成像技术，以评估视网膜，脉络膜和薄片cribrosa的细胞水平的变化，这些研究将是 通过电子显微镜检查深视神经头的椎板膜的超微结构研究。 为了特别评估近视眼是否更容易受到青光眼的影响，使用Microbeads（Microbead遮挡模型）及其对结构和功能评估的影响，IOP将在正常和近视眼中升高IOP。在青光眼中，视网膜细胞，视网膜敏感性降低，而lamina cribrosa和副毛皮巩膜会经历结构畸形。如上所述，将评估正常的眼睛和近视眼，并将通过轴向长度和折射率分析青光眼损伤程度。 该项目代表了在近视动物模型中诱导青光眼的首次尝试并在同一眼睛中进行评估，这两个疾病过程中已知的结构和功能都受到影响。它将提供机会寻找结构变化的功能相关性。除了对这些条件提供新的见解外，他们的预防和治疗方法是合理的结果。 该项目将在克里斯汀·怀尔德索特（Christine Wildsoet）博士的指导下进行，他在膜化和近视眼增长领域具有广泛的知识，并接受了验光和药理学的培训。三位高级视力科学家还同意担任这项工作方面的顾问：1）摩术专家劳拉·弗里什曼（Laura Frishman）（休斯顿大学），他们将协助精炼隔离视网膜内部途径的协议 豚鼠，2）Austin Roorda博士（Cal。Berkeley），他同意为视网膜成像和图像分析提供指导，以及3）Ronald Harwerth博士（休斯顿大学），他将在改进实验性绿oc糖瘤模型方案方面提供建议。 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。高近视可导致失明，并且与青光眼的风险增加有关。该建议旨在描述镜头诱发的近视​​的结构和功能性眼变化，并寻找与高高的青光眼IOP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。