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: 10593149
• 负责人: Joel R Palko
• 金额: $ 32.7万
• 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/10593149
• 关键词: Advanced Development; Affect; Animal Model; Award; Axon; Axonal Transport; Biomechanics; Blindness; Blood Vessels; Blood flow; Cannulations; 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; Papillary; 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 项目总结/摘要 青光眼是世界范围内不可逆性失明的主要原因。眼内压（IOP），唯一已知的 青光眼的可改变的危险因素，被确定为视网膜神经节细胞死亡的一个致病变量， 视神经头（optic nerve head，ONH）然而，IOP如何与ONH相互作用以产生 昏迷性损伤。有证据表明，IOP对ONH产生直接机械损伤， 通过减少流向ONH的血液而造成缺氧损伤。我们目前对如何理解 IOP升高期间ONH结缔组织的机械变形影响血管系统， 存在于这个眼部区域这个提议的假设是， 在ONH内和周围的压缩将证明ONH灌注速度的更大降低， IOP升高。为了验证这一假设，我们开发了新的超声成像技术， 组织应变（变形）和灌注速度的测量在该区域内的共定位 ONH，发生昏迷性损伤。拟议的目标将表明ONH在多大程度上 结缔组织应变影响到ONH的灌注率，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。初步结果使用创新的 成像系统已经显示出在包含小动脉的神经周围巩膜区域内的局部应变， 供应ONH。这些初步的研究证明了这种技术测量灌注速度的能力 在筛板的深度内，眼睛的一个区域不能使用当前的光学系统测量。 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。 在确定视乳头周围巩膜的硬化是否改善ONH灌注的同时测量应变幅度。在目标2中，a 将使用具有受控IOP升高的啮齿动物模型来确定视乳头周围巩膜的体内作用 ONH灌注和轴突运输阻断的硬化。这些信息将进一步加深我们对 青光眼的病理生理学，并检查潜在的临床前治疗策略， 降低灌注压。这项研究计划是在一个 多学科导师团队。在此期间获得的专业发展和初步数据 这段时间将使我能够实现我的职业目标，成为一名拥有独立R 01资助奖项的医生-科学家 在这一领域的眼睛研究。