Myopia and Glaucoma, Linked via Mechanotransduction Mechanisms Affecting the Ganglion Cell Complex

近视和青光眼通过影响神经节细胞复合体的机械传导机制联系起来

• 批准号: 10656793
• 负责人: Alexandra Benavente-Perez
• 金额: $ 40.88万
• 依托单位: STATE COLLEGE OF OPTOMETRY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656793
• 关键词: Acceleration; Acute; Address; Affect; Anatomy; Animal Model; Architecture; Astrocytes; Blindness; Cell Count; Cell Survival; Cell physiology; Cells; Complex; Connexin 43; Coupling; Data; Detection; Development; Diagnosis; Early identification; Epidemic; Epidemiologist; Etiology; Exhibits; Exposure to; Eye; Functional disorder; Genetic; Genetic Markers; Glaucoma; Goals; Growth; Health Professional; Human; Impairment; Individual; Intervention; Investigational Therapies; Link; Masks; Mechanical Stress; Mechanics; Microglia; Mission; Modeling; Molecular; Myopia; Nature; Neuroglia; Neuropathy; Optic Disk; Outcome; Patients; Pattern; Perception; Population; Predisposition; Prevalence; Prevention strategy; Progressive Myopia; Public Health; Quality of life; Research; Retinal Ganglion Cells; Risk; Scientist; Secondary to; Signal Pathway; Signal Transduction; Smoker; Stretching; Stroke; Testing; Therapeutic; Thick; Thinness; Time; Tissues; Vision; Visual impairment; axon injury; axonal degeneration; cardiovascular disorder risk; diagnostic biomarker; diagnostic strategy; early detection biomarkers; experience; ganglion cell; glial activation; hypertensive; improved; innovation; mechanical stimulus; mechanotransduction; neuroprotection; nonhuman primate; novel; pharmacologic; pressure; prevent; response; stressor; therapeutic target; tool; treatment strategy

Project Summary/Abstract Public perception of myopia as a simple inconvenience masks its sight-threatening consequences. Even moderate levels of myopia predispose an individual to glaucoma at rates equal to a hypertensive's risk for cardiovascular disease. Yet, we lack specific diagnostic markers to identify glaucoma in myopic patients. In fact, myopic eyes can exhibit anatomical changes difficult to distinguish from glaucoma. This is alarming because half the world population is predicted to be myopic in 30 years, which will increase significantly the global prevalence of myopic glaucoma and associated visual impairment. Glaucoma is a complex neuropathy that preferentially affects the ganglion cell complex (GCC). Myopia results in significant eye growth, and appears related to glaucoma through its effect on the optic nerve head. However, the mechanisms that link myopia and glaucoma, in particular the effect of myopic growth on the GCC, remain unexplored. We hypothesize that glaucoma and myopia are linked via mechanisms that sense and respond to mechanical stimuli and affect the GCC. The long-term goal of this research is to identify the mechanisms of myopic glaucoma and explore novel neuroprotection therapeutics to prolong ganglion cell function and survival. The overall objectives in this application are to identify early 1) genetic, 2) cellular, 3) structural and 4) functional markers of glaucoma longitudinally as experimental eyes develop progressive myopia compared to eyes induced with glaucoma. The research proposed in this application is innovative because it focuses on identifying key hallmarks of glaucoma comparing unique animal models of myopia and glaucoma that mimic the prolonged exposure to sustained eye growth experienced by human myopic eyes over time, which is fundamental to understanding how glaucoma can originate from myopia. This research will have a direct positive impact as a tool to accelerate the development of novel prevention and diagnostic strategies for myopic glaucoma, and open up new research avenues for pharmacological interventions and experimental therapeutics to prevent glaucomatous impairment in myopic eyes. The proposed research is significant because is expected to provide strong evidence of the unknown nature of the myopia-glaucoma relationship, will help clinicians address the long-standing challenge of diagnosing glaucoma in myopic eyes, epidemiologists refine distribution patterns of myopic glaucoma, public health professionals develop prevention strategies and campaigns, and scientists create new research avenues for myopic glaucoma.

项目摘要/摘要 公众认为近视是一种简单的不便，掩盖了它对视力的威胁 后果。即使是中等程度的近视也容易患上青光眼。 相当于高血压患心血管疾病的风险。然而，我们缺乏特定的诊断标记。 目的：识别近视患者中的青光眼。事实上，近视眼可以表现出解剖学上的变化。 很难与青光眼相鉴别。这是令人震惊的，因为世界上一半的人口 预计将在30年内近视，这将显著增加全球近视的患病率 近视性青光眼及其相关视力损害。青光眼是一种复杂的神经病变， 优先影响神经节细胞复合体(GCC)。近视会导致显著的眼睛生长， 通过其对视神经头的影响，似乎与青光眼有关。然而， 近视与青光眼的联系机制，特别是近视发育对GCC的影响， 仍未被开发。我们假设青光眼和近视是通过 感觉并对机械刺激做出反应，影响GCC。这项研究的长期目标是 是确定近视性青光眼的发病机制并探索新的神经保护疗法 延长神经节细胞功能和存活时间。此应用程序的总体目标是 识别青光眼的早期1)遗传、2)细胞、3)结构和4)功能标志 与实验眼相比，实验眼纵向发展为进行性近视 青光眼。本申请中提出的研究具有创新性，因为它侧重于 识别青光眼的关键特征比较近视和青光眼的独特动物模型 这模拟了人类近视眼睛经历的持续眼睛生长的长期暴露 随着时间的推移，这是理解青光眼如何起源于近视的基础。这 研究作为加速小说发展的工具，将产生直接的积极影响 近视性青光眼的预防和诊断策略，开辟新的研究途径 用于药物干预和实验治疗以预防青光眼 近视眼的损害。拟议的研究具有重要意义，因为预计将提供 近视-青光眼关系的未知性质的有力证据将有助于临床医生 解决诊断近视眼青光眼的长期挑战，流行病学家 完善近视性青光眼的分布模式，公共卫生专业人员制定预防措施 战略和活动，科学家创造了近视性青光眼的新研究途径。