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)：眼生物力学对视神经头灌注的影响，Palko，PL 项目摘要/摘要 青光眼是世界范围内导致不可逆转失明的主要原因。眼压(IOP)，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 视神经头(ONH)。然而，IOP如何与ONH相互作用产生 青光眼损害。有证据表明，眼压会对ONH产生直接的机械损伤，并 由于流向ONH的血液减少而造成的缺氧性损害。在我们目前的理解中存在着一个缺口 眼压升高时ONH结缔组织的机械变形影响血管系统 位于这个眼球区域内。这项提议的假设是，表现出更大组织的眼睛 在ONH内和周围的压缩将显示ONH的灌流速度在 眼压升高。为了验证这一假设，我们开发了新的超声成像技术，允许 组织应变(变形)和血流速度测量的共同定位 哦，青光眼损害的地方。拟议的目标将表明ONH在多大程度上 结缔组织张力影响ONH的灌注率，并决定是否化学硬化 在眼压升高期间，ONH周围的巩膜将改善眼压的灌注量。使用创新的 成像系统显示神经周围巩膜内含有微动脉的局部应变 供应ONH。这些初步研究证实了这种技术测量血流速度的能力。 在筛板的深度内，眼睛的一个区域，不能用当前的光学方法测量 方法：研究方法。在目标1中，我们将评估眼灌注压、灌流速度和组织之间的相互作用。 在确定乳头周围巩膜硬化是否改善ONH血流时，应力值。在目标2中，一个 可控制眼压升高的啮齿动物模型将被用来确定乳突周围巩膜的体内效应 ONH灌流僵硬和轴突运输阻断。这一信息将加深我们对 青光眼的病理生理学和潜在的临床前治疗策略 降低了灌流压力。这项研究计划是在一个 多学科导师团队。获奖期间获得的职业发展和初步数据 这段时间将使我能够实现我的职业目标，成为一名内科科学家，并获得独立的R01资助奖项 在这个眼科研究领域。