Cellular, molecular and physical mechanisms of vitreous structural heterogeneity underlying posterior vitreous detachment

玻璃体后脱离的玻璃体结构异质性的细胞、分子和物理机制

• 批准号: 10740173
• 负责人: Eileen S Hwang
• 金额: $ 19.02万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740173
• 关键词: Address; Advisory Committees; Affect; Age; Aging; Animal Model; Area; Award; Biochemistry; Biological; Cell Culture Techniques; Cells; Cold Therapy; Collagen; Collagen Fiber; Collagen Type II; Collagen Type IX; Complement; Computer Models; Data; Degradation Pathway; Deterioration; Digestion; Etiology; Excision; Experimental Models; Eye; Eye Movements; Fiber; Future; Gases; Goals; Heterogeneity; Human; Image Analysis; Imaging Techniques; Incidence; Incubated; Individual; International; Intervention; Knock-out; Knowledge; Leadership; Licensing; Link; Macrophage; Mechanics; Mentors; Methods; Modeling; Molecular; Morbidity - disease rate; Motion; Mus; Oryctolagus cuniculus; Pathway interactions; Posterior Vitreous Detachments; Prevention strategy; Process; Proteins; Quality of life; Research; Research Personnel; Retina; Retinal Detachment; Role; Specificity; Structure; Surface; Surgeon; System; Testing; Therapeutic Studies; Translational Research; United States; Vision; Visualization; Work; age related; aged; career development; collagenase; density; experimental study; high risk population; innovation; light scattering; member; novel strategies; novel therapeutics; prevent; quantitative imaging; reflectance confocal microscopy; research study; skills; targeted treatment

PROJECT SUMMARY/ABSTRACT This is a K08 award application for Dr. Eileen Hwang, a licensed vitreoretinal surgeon, to independently conduct research studies to identify mechanisms of vitreous aging. The K08 will provide her the support necessary to acquire critical skills in four key career development areas: 1) rabbit models of posterior vitreous detachment; 2) cell-matrix interactions and mechanics; 3) quantitative image analysis; and 4) translational research leadership. To achieve her goals, Dr. Hwang has assembled an interdisciplinary mentoring team comprised of Dr. Brittany Coats (Primary Mentor), an expert in vitreous mechanics, and two Co-Mentors: Dr. Paul Bernstein, an internationally recognized researcher of retinal biochemistry, and Dr. Bryan Jones, a pioneer in retinal connectomics. Complementing these mentors, Dr. Hwang also has a 3 member advisory committee to support her goal of developing models and methods for investigating vitreous aging. Retinal detachment leads to significant morbidity and impacts on quality of life, and new strategies for prevention in high-risk individuals are necessary. There is a critical need to elucidate the mechanisms of posterior vitreous detachment (PVD), the primary cause of retinal detachment. Dr. Hwang's objective is to address the gaps in current knowledge about vitreous structure and aging. Her research will result in preliminary data and models to support future proposals investigating whether biological manipulation of vitreous structure can affect PVD in rabbit models. She proposes the following Specific Aims: Aim 1] Identify the effect of decreasing type IX collagen on vitreous structure; Aim 2] Determine the role of hyalocytes in vitreous aging; and Aim 3] Establish the relationships between eye motion, structural heterogeneity, and PVD. The proposed research is significant because it will: 1) determine whether age-related loss of type IX collagen and increased hyalocyte degradation are pathways that could be blocked to prevent PVD and prevent retinal detachment in high risk individuals, and 2) develop cell culture and animal models of vitreous aging to enable mechanistic and therapeutic studies. The proposed research is innovative because it will apply cellular and molecular specificity to inhibit PVD.

项目概要/摘要 这是注册玻璃体视网膜外科医生 Eileen Hwang 博士的 K08 奖项申请，独立 进行研究以确定玻璃体老化的机制。 K08将为她提供支持 获得四个关键职业发展领域的关键技能所必需的：1）兔后玻璃体模型 分离; 2）细胞-基质相互作用和力学； 3）定量图像分析； 4）翻译 研究领导力。为了实现她的目标，黄博士组建了一支跨学科的指导团队 由玻璃体力学专家 Brittany Coats 博士（主要导师）和两位共同导师组成： 国际公认的视网膜生物化学研究员保罗·伯恩斯坦 (Paul Bernstein) 和视网膜生物化学专家布莱恩·琼斯 (Bryan Jones) 博士 视网膜连接组学的先驱。作为对这些导师的补充，黄博士还拥有 3 名顾问 委员会支持她开发研究玻璃体老化的模型和方法的目标。 视网膜脱离会导致严重的发病率并影响生活质量，因此需要采取新策略 对高危人群进行预防是必要的。迫切需要阐明其机制 玻璃体后脱离（PVD），视网膜脱离的主要原因。黄博士的目标是 弥补当前关于玻璃体结构和老化的知识空白。她的研究将导致 初步数据和模型，以支持未来的提案，调查是否生物操纵 玻璃体结构会影响兔子模型中的 PVD。她提出了以下具体目标： 目标 1] 确定 IX型胶原蛋白减少对玻璃体结构的影响；目标 2] 确定透明细胞在 玻璃体老化；目标 3] 建立眼球运动、结构异质性和 PVD ​​之间的关系。 拟议的研究意义重大，因为它将：1）确定是否与年龄相关的 IX 型丧失 胶原蛋白和增加的透明细胞降解是可以阻断的途径，以预防 PVD ​​和预防 高危人群的视网膜脱离，2) 开发玻璃体老化的细胞培养和动物模型 实现机制和治疗研究。拟议的研究具有创新性，因为它将应用细胞 和抑制PVD的分子特异性。