Optic Nerve Aging and Glaucoma

视神经老化和青光眼

• 批准号: 8916122
• 负责人: Thasarat Vajaranant
• 金额: $ 23.54万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8916122
• 关键词: Activities of Daily Living; Address; Affect; Age; Aging; Area; Automobile Driving; Basic Science; Bilateral oophorectomy; Biometry; Biostatistical Methods; Blindness; Career Choice; Clinic; Clinical; Cohort Studies; Collaborations; Control Groups; Data; Diagnostic; Educational Status; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Estradiol; Estrogen Antagonists; Estrogen Therapy; Estrogens; Evaluation; Excision; Fostering; Foundations; Future; Glaucoma; Goals; Gonadal Steroid Hormones; Health; Healthcare; Hormonal; Image; Individual; Investigation; Knowledge; Lead; Life; Longevity; Malignant Neoplasms; Measures; Medical Records; Menopause; Mental Depression; Mentors; Modeling; Motor Vehicles; Nerve Degeneration; Nerve Fibers; Optic Nerve; Optical Coherence Tomography; Optics; Ovariectomy; Ovary; Participant; Perfusion; Photophobia; Physiologic Intraocular Pressure; Population; Predisposition; Preventive Intervention; Primary Open Angle Glaucoma; Public Health; Publishing; Reading; Reporting; Research; Research Proposals; Research Training; Retina; Retinal; Retinal Ganglion Cells; Risk; Risk Factors; Role; Scientist; Selective Estrogen Receptor Modulators; Sex Characteristics; Structure; Testing; Therapeutic Intervention; Training; Training Programs; United States; Visual Acuity; Visual Fields; Visual impairment; Walking; Woman; Work; age group; age related; aged; base; cancer therapy; cohort; effective intervention; falls; functional loss; improved; indexing; inhibitor/antagonist; men; novel; novel diagnostics; pressure; programs; prospective; research study; screening; sex; translational study; vehicular accident

DESCRIPTION (provided by applicant): Glaucoma, the leading cause of irreversible blindness in the United States and worldwide, remains a major global public health concern. Primary open-angle glaucoma (POAG), age-dependent and intraocular pressure (IOP)-related neurodegeneration of the optic nerve comprises 74% of all types of glaucoma. Glaucoma-related visual loss, even in the presence of normal visual acuity, can lead to significant functional visual impairment and substantial secondary risks to health including depression, falls and motor vehicle accidents. Approximately 3% percent of the world population aged 40 years and older has glaucoma. Worldwide, women comprise 59% of those affected by glaucoma, due in large part to their greater longevity. Women are also at risk for visual loss from glaucoma because they are 24% less likely to be treated for this condition, and some data suggest that women report greater functional loss from glaucoma than men. These sex differences underscore the importance of investigating sex-specific risk factors for glaucoma. To that end, this application builds on a conceptual model and preliminary epidemiological data to explore the novel idea that early loss of estrogen might contribute to early aging of the optic nerve in women and thereby increase women's risk of developing glaucoma. Clinical, epidemiological, and basic science studies indicate that estradiol has neuroprotective effects on the optic nerve. The training and research proposals in this application are aimed at fostering the career path of an independent clinician-scientist who will lead a scholarly program of research that examines factors associated with optic nerve aging and the role of sex steroid hormones, particularly estradiol, in the degeneration of the optic nerve and risk for glaucoma. A proposed five-year program of training and research includes: 1) applying MPH-level training in epidemiological and biostatistical methods to examine the impact of early oophorectomy on glaucoma risk in a large epidemiological cohort study of the health consequences of oophorectomy; and 2) applying training in epidemiologic methods, biostatistics, clinical imaging and sex steroid hormones to a mechanistic, translational study aimed at comparing measures of optic nerve aging, as indexed by thinning of the retinal nerve fiber by optical coherence tomography and decreased light sensitivity by visual field testing in women who underwent early oophorectomy and age-matched controls. This work will guide further research in early glaucoma screening and treatment of women with early natural menopause (approximately 6% of women) and early bilateral oophorectomy (37% of women who undergo bilateral oophorectomy). This training and line of research will provide a foundation for future studies investigating the effects of aromatas inhibitors, selective estrogen receptor modulators and other anti- estrogen treatments on the optic nerve. More broadly, this work serves as a foundation for a future line of investigations int sex-differences and non-hormonal mechanisms of optic nerve aging and risks for glaucoma.

描述（由申请人提供）：青光眼是美国和世界范围内不可逆失​​明的主要原因，仍然是全球公共卫生的主要关注点。原发性开角青光眼（POAG），年龄依赖性和眼内压（IOP）相关的神经变性，占所有类型的青光眼的74％。即使存在正常视力，与青光眼相关的视觉丧失也可能导致严重的功能性视觉障碍和对健康的重大次要风险，包括抑郁症，跌倒和机动车事故。大约3％的40岁及以上的世界人口患有青光眼。在全球范围内，女性占受青光眼影响的女性的59％，这在很大程度上是由于她们的寿命更长的寿命。妇女还处于因青光眼视觉损失而有风险，因为患有这种情况的可能性低24％，并且一些数据表明，女性报告的功能损失比男性更大。这些性别差异强调了研究性别危险因素对青光眼的重要性。为此，该应用是建立在概念模型和初步流行病学数据的基础上，以探讨以下新想法，即雌激素的早期丧失可能会导致女性视神经的早期衰老，从而增加女性患青光眼的风险。临床，流行病学和基础科学研究表明，雌二醇对视神经具有神经保护作用。本应用程序中的培训和研究建议旨在促进独立的临床医生 - 科学家的职业道路，他将领导一项学术研究计划，研究与视神经衰老相关的因素以及性类固醇激素的作用，尤其是雌二醇，尤其是雌二醇，在视神经的退化和glaucoma的风险中。拟议的五年培训和研究计划包括：1）在流行病学和生物统计学方法中应用MPH级培训，以检查早期卵巢切除术对青光眼风险的影响，以在大型流行病学共同研究中对卵形切除术的健康后果进行研究； 2）在流行病学方法，生物统计学，临床成像和性类固醇激素中应用培训，旨在比较视神经纤维纤维纤维纤维的措施，通过光学神经纤维纤维的稀疏来比较视网膜神经纤维纤维的磨损，并通过光学相干性层析成像和弱视症状的近视敏感性和年龄段的近视效果良好的妇女良好的妇女友好的妇女友善症状。这项工作将指导对早期青光眼筛查和治疗早期自然早期（约6％的女性）和双侧卵巢切除术（37％接受双侧卵巢切除术的女性）的进一步研究。这项培训和研究线将为未来研究的基础研究，研究芳香族抑制剂，选择性雌激素受体调节剂和其他抗衰老对视神经的影响。更广泛地说，这项工作为未来的调查范围内的性别差异和视神经衰老的非激素机制和青光眼风险的非激素机制提供了基础。