The Effect of Estrogen Deficiencies on Vision Loss in Glaucoma

雌激素缺乏对青光眼视力丧失的影响

• 批准号: 10382223
• 负责人: Andrew J Feola
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382223
• 关键词: Affect; Age; Anatomy; Animals; Attention; Attenuated; Axon; Biomechanics; Blindness; Brain; Cartilage; Cell Survival; Cell physiology; Cervix Uteri; Clinical; Clinical Trials; Complement; Connective Tissue; Contrast Sensitivity; Data; Development; Disease; Electroretinography; Environment; Estrogen Metabolism; Estrogen Receptors; Estrogen Therapy; Estrogens; Etiology; Experimental Models; Exposure to; Eye; Female; Future; Gelatinase A; Gelatinase B; Gender; General Population; Genetic Polymorphism; Glaucoma; Goals; Health; Image; Individual; Inflammation Mediators; Inflammatory; Interleukin-6; Lead; Link; Matrix Metalloproteinases; Measures; Mechanics; Menopause; Mentorship; Metabolic Pathway; Modeling; Monitor; Mutation; Norway; Ocular Hypertension; Optic Disk; Optical Coherence Tomography; Pathway interactions; Patients; Pattern; Peptide Hydrolases; Persons; Physiologic Intraocular Pressure; Play; Population; Postmenopause; Predisposition; Premature Menopause; Premenopause; Property; Protease Inhibitor; Rattus; Reporting; Research; Research Personnel; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; System; TNF gene; Testing; Therapeutic; Time; Tissues; Training; Vagina; Veterans; Vision; Visual Acuity; Visual Fields; Visual impairment; Woman; World Health Organization; aged; biomechanical test; bone; conventional therapy; inflammatory marker; inhibitor therapy; insight; interdisciplinary approach; juvenile animal; male; mechanical properties; military veteran; novel therapeutics; post-doctoral training; preservation; prevent; rehabilitation research; research and development; tonometry; tool; visual dysfunction; visual information; visual neuroscience

Glaucoma is the largest cause of irreversible blindness in the world and is characterized by the loss of retinal ganglion cells (RGCs), which transmit visual information from the eye to the brain. While the exact cause of glaucoma is unknown, recent evidence has shown that early menopause in women is linked with developing glaucoma. Further, mutations in estrogen receptors and polymorphisms in the estrogen metabolic pathway are linked with glaucoma in both genders. However, since the number of woman veterans has nearly doubled in the last ten years, the VA recently formed the Women’s Veterans Health Research Network (WVHRN) to help focus attention on research and treatments for this increasing population in the veteran population. These data highlight that estrogen plays a vital role in the development of glaucoma and is an important issue in the VA; however, the mechanism(s) underlying estrogen’s effects are unknown. We hypothesize that an estrogen deficiency contributes to the etiology of glaucoma by altering ocular biomechanics, increasing an individual’s risk for developing glaucoma. In this study, we will investigate the link between estrogen and glaucoma through three Specific Aims. In our first specific aim, we will measure the impact of menopause on ocular compliance and scleral mechanical properties in pre- and post-menopausal young (3-4 month) and aged (9-10 month) female rats. This will allow us to assess how estrogen deficiencies alter the biomechanical properties of the eye, which may impact RGC survival. In our second specific aim, we will evaluate the effect of early and late menopause in rats with experimental glaucoma/ocular hypertension. Specifically, over 12 weeks, we will investigate functional visual impairment (e.g. visual acuity and contrast sensitivity), RGC function and anatomical changes in the eye due to experimental glaucoma. Further, we will investigate the potential therapeutic benefits of estrogen in female and male rats with experimental glaucoma. This will allow us to determine whether estrogen therapy can preserve visual function after inducing experimental glaucoma. Our third specific aim will examine the impact of menopause on inflammatory markers and protease expression in the eye. We will also assess if the inhibition of inflammatory and protease expression prevents changes in ocular compliance associated with menopause. This investigates the potential mechanism(s) that an estrogen deficiency induces changes in ocular biomechanical properties. Our preliminary data support this overall hypothesis. We expect to build off these strong data and find that menopause will differentially influence the biomechanical properties of the eye, with young animals having a larger impact from an estrogen deficiency. We also anticipate finding that post-menopausal rats have more severe visual impairment compared to pre-menopausal rats and that estrogen therapy will preserve visual function in post-menopausal females and aged male with experimental glaucoma. Lastly, we believe that menopause will increase inflammatory markers and protease expression and that inhibiting these changes after menopause will preserve ocular biomechanical properties. These data will provide the first clear picture of how estrogen modulates the risk of developing glaucoma. If we are successful in our aims, these finding will motivate the development of estrogen as a novel therapeutic treatment for glaucoma. Overall, this study will provide information on how estrogen is linked to glaucoma and motive us to develop future studies that will investigate estrogen as a novel therapeutic treatment for glaucoma of female and male veterans in the VA clinical population. This meets the Rehabilitation Research and Development goal of preventing and treating vision loss. This CDA2 will aid in the ongoing training of the postdoctoral candidate to become an independent and successful investigator in the fields of visual neuroscience, biomechanics and glaucoma within the VA environment.

青光眼是世界上不可逆失明的最大原因，其特征是视网膜丧失 神经节细胞（RGC），而确切的原因。 青光眼是未知的，最近的证据表明，女性的早期更年期与发展有关 青光眼。 但是，与两种性别的青光眼有关。 在过去的十年中，弗吉尼亚州最近成立了妇女退伍军人健康研究网络（WVHRN） 将这些数据的人口的研究和治疗重点 强调雌激素在青光眼的发展中起着至关重要的作用，并且在VA中很重要。 但是，雌激素效应的基础机制是未知的。 缺乏症有助于替代生物力学的青光眼病因，增加了ANN 个人患青光眼的风险。 青光眼在我们的第一个特定目标中的三个特定目标 少年后和少年后（3-4个月）和 年龄（9-10个月）的雌性大鼠。 眼睛的特性，可能会影响我们的第二个特定目的的RGC生存。 具有实验性青光眼/眼高血压的大鼠早期和晚期的早期和晚期。 几周，我们将研究功能性视觉障碍（例如视力和对比度灵敏度），RGC 由于实验性青光眼引起的功能和解剖学变化。 雌激素的潜在治疗疗法在雌性和男性大鼠中具有允许 我们确定雌激素疗法在诱导实验青光眼后是否可以保留视觉功能。 我们的第三个特定目标将检查更年期对炎症标记和蛋白酶的影响 在眼中的表达。 与更年期相关的眼部依从性的变化。 雌激素缺乏引起眼部生物力学特性的变化。 总体假设。 影响眼睛的生物力学特性，年轻动物对雌激素产生更大的影响 缺乏症。 与绝经前大鼠相比，雌激素疗法将保留绝经后的视觉功能 女性和老年男性具有实验性青光眼。 炎症标志物和蛋白酶Expresseon和Thibiting Thibiting Thibiting thitter Menopause将会 保存眼镜的生物力学特性。 调节发展青光眼的风险。 雌激素作为青光眼的一种新的治疗疗法的发展。 有关雌激素如何与青光眼相关的信息，并动机我们开发未来的研究，这些研究将研究 在VA临床中，女性和男性退伍军人的青光眼的雌激素高达高达高端的雌激素 人口。 损失。这个CDA2将有助于持续的候选人成为依赖的人 在VA内的视觉神经科学，生物力学和青光眼领域的成功研究者 环境。