Influence of Ocular Biomechanics on Optic Nerve Head Perfusion

眼生物力学对视神经乳头灌注的影响

• 批准号: 10334880
• 负责人: Joel R Palko
• 金额: $ 32.96万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-20 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10334880
• 关键词: Advanced Development; Affect; Animal Model; Award; Axon; Axonal Transport; Biomechanics; Blindness; Blood Vessels; Blood flow; Cell Death; Centers of Research Excellence; Cessation of life; Chemicals; Collagen; Connective Tissue; Data; Development; Diagnosis; Disease; Environment; Event; Eye; Family suidae; Foundations; Functional disorder; Funding; Glaucoma; Goals; Hour; Hypoxia; Imaging Techniques; Impairment; Individual; Ischemia; Label; Manipulative Therapies; Measurement; Measures; Mechanics; Mediating; Mentors; Mentorship; Methodology; Microbubbles; Modeling; Optic Disk; Optic Nerve; Optical Methods; Penetration; Perfusion; Persons; Physicians; Physiologic Intraocular Pressure; Predisposition; Rattus; Rattus norvegicus; Research; Retinal Ganglion Cells; Risk Factors; Rodent Model; Role; Scientist; Sclera; System; Systemic blood pressure; Techniques; Technology; Testing; Therapeutic; Thick; Tissues; Ultrasonography; Visualization; anterior chamber; arteriole; career; crosslink; effective therapy; genipin; imaging system; improved; in vivo; innovation; insight; mechanical properties; modifiable risk; multidisciplinary; novel; novel strategies; ocular imaging; ophthalmic artery; perineural; pre-clinical; pressure; prevent; programs; response; retinal ganglion cell degeneration; therapeutic evaluation; treatment strategy; ultrasound; vision science

Project 004 (459): Influence of Ocular Biomechanics on Optic Nerve Head Perfusion, Palko, PL PROJECT SUMMARY/ABSTRACT Glaucoma is the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP), the only known modifiable risk factor for glaucoma, is established as a causative variable in the death of retinal ganglion cells at the optic nerve head (ONH). However, it remains to be discovered how IOP interacts with the ONH to produce glaucomatous damage. Evidence suggests that IOP produces direct mechanical damage to the ONH and hypoxic damage by a reduction in blood flow to the ONH. There is a gap in our current understanding of how mechanical deformations of the ONH connective tissue during elevations in IOP influence the vasculature that resides within this ocular region. The hypothesis of this proposal is that eyes that demonstrate greater tissue compression within and around the ONH will demonstrate a greater reduction in ONH perfusion velocity during elevations of IOP. To test this hypothesis, we have developed novel ultrasound imaging techniques that permit the colocalization of measurements of tissue strain (deformation) and perfusion velocity within the region of the ONH, where glaucomatous damage occurs. The proposed aims will demonstrate the degree to which ONH connective tissue strain influences the perfusion rates to the ONH and determine if chemically stiffening the sclera around the ONH will improve perfusion during IOP elevations. Preliminary results using an innovative imaging system have shown localized strain within regions of the perineural sclera containing arterioles that supply the ONH. These initial studies demonstrate the ability of this technique to measure the perfusion velocity within the depth of the lamina cribrosa, a region of the eye that cannot be measured using current optical methods. In Aim 1, we will evaluate the interplay between ocular perfusion pressure, perfusion velocity and tissue strain magnitudes while determining if stiffening of the peripapillary sclera improves ONH perfusion. In Aim 2, a rodent model with a controlled IOP elevation will be used to ascertain the in vivo effect of peripapillary scleral stiffening on ONH perfusion and axonal transport blockade. This information will further our understanding of glaucoma pathophysiology and examine a potential pre-clinical treatment strategy for glaucomatous eyes with reduced perfusion pressures. This research plan was developed with the assistance and support of a multidisciplinary team of mentors. The professional development and preliminary data gained during this award period will enable me to achieve my career goal as a physician-scientist with an independent R01-funded award in this field of ocular research.

项目 004 (459)：眼部生物力学对视神经头灌注的影响，Palko，PL 项目概要/摘要 青光眼是全世界不可逆转失明的主要原因。眼压（IOP）是唯一已知的 青光眼的可改变危险因素，被确定为视网膜神经节细胞死亡的致病变量 视神经乳头 (ONH)。然而，IOP 如何与 ONH 相互作用以产生仍有待发现 青光眼损伤。有证据表明 IOP 对 ONH 产生直接机械损伤 ONH 血流量减少造成缺氧损伤。我们目前对如何做到这一点的理解存在差距 眼压升高期间 ONH 结缔组织的机械变形会影响脉管系统 位于该眼部区域内。该提议的假设是，眼睛表现出更大的组织 ONH 内部和周围的压缩将表现出 ONH 灌注速度的更大降低 眼压升高。为了检验这一假设，我们开发了新颖的超声成像技术，可以 组织应变（变形）和灌注速度测量的共定位 ONH，发生青光眼损伤的地方。拟议的目标将证明 ONH 的程度 结缔组织应变影响 ONH 的灌注速率，并确定是否化学硬化 ONH 周围的巩膜将改善 IOP 升高期间的灌注。使用创新的初步结果 成像系统显示出含有小动脉的神经周围巩膜区域内的局部应变 供应ONH。这些初步研究证明了该技术测量灌注速度的能力 在筛板深度内，这是目前光学无法测量的眼睛区域 方法。在目标 1 中，我们将评估眼灌注压、灌注速度和组织之间的相互作用 应变大小，同时确定视乳头周围巩膜的硬化是否改善 ONH 灌注。在目标 2 中， 具有受控眼压升高的啮齿动物模型将用于确定视乳头周围巩膜的体内效果 ONH 灌注硬化和轴突运输阻断。这些信息将加深我们对 青光眼病理生理学并检查青光眼潜在的临床前治疗策略 降低灌注压。本研究计划是在以下机构的协助和支持下制定的 多学科导师团队。此次获奖期间获得的专业发展和初步数据 期间将使我能够实现作为一名医师科学家的职业目标，并获得独立的 R01 资助的奖项 在眼科研究这一领域。