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 公众对近视的看法是一种简单的不便掩盖，这威胁了视力 结果。即使是中等水平的近视水平，易于以青光眼易于 等于高血压患心血管疾病的风险。但是，我们缺乏特定的诊断标记 鉴定近视患者的青光眼。实际上，近视眼可以表现出解剖学变化 很难与青光眼区分开。这令人震惊，因为世界一半的人口是 预计在30年内将是近视，这将大大增加 近视青光眼和相关的视觉障碍。青光眼是一种复杂的神经病 优先影响神经节细胞复合物（GCC）。近视导致眼睛显着生长， 并通过对视神经头的影响与青光眼有关。但是， 将近视和青光眼联系起来的机制，特别是近视生长对海湾合作委员会的影响， 保持未探索。我们假设青光眼和近视是通过机制连接的 感知并应对机械刺激并影响海湾合作委员会。这项研究的长期目标 是识别近视青光眼的机制并探索新型的神经保护疗法 延长神经节细胞功能和存活。此应用程序中的总体目标是 识别早期1）遗传，2）细胞，3）结构和4）青光眼的功能标志物 与诱发的眼睛相比 青光眼。本应用程序中提出的研究是创新的，因为它专注于 识别青光眼的关键标志，比较近视和青光眼的独特动物模型 模仿人类近视的长期暴露于持续的眼睛生长 随着时间的流逝，这对于了解青光眼如何起源于近视是至关重要的。这 研究将有直接的积极影响，作为加速新颖的发展的工具 预防和近视青光眼的诊断策略，并开放新的研究途径 用于药理干预措施和实验治疗剂，以防止青光眼 近视眼中的损害。拟议的研究很重要，因为期望 有力的有力证据表明近视糖果关系的未知性质将有助于临床医生 解决近视眼诊断青光眼的长期挑战，流行病学家 公共卫生专业人员的近视青光眼的精炼分配模式开发预防 战略和运动，科学家为近视青光眼创造了新的研究途径。