Pressure Induced Dynamic 3D Changes in Lamina Cribrosa

压力引起的筛板动态 3D 变化

• 批准号: 7492062
• 负责人: DONALD J BROWN
• 金额: $ 22.42万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492062
• 关键词: 3-Dimensional; Age; Algorithms; Anatomy; Autopsy; Axon; Blindness; Cessation of life; Collagen; Confocal Microscopy; Cornea; Depth; Development; Disease; Elderly; Ethnic Origin; Eye; Glaucoma; Histological Techniques; Human; Image; Individual; Injury; Invasive; Lasers; Length; Location; Measurement; Mechanics; Methods; Microscopy; Movement; Optic Disk; Pathologic Processes; Physiologic Intraocular Pressure; Physiologic pulse; Principal Investigator; Property; Pulse taking; Refractive Errors; Resolution; Retinal Ganglion Cells; Risk Factors; Shapes; Signal Transduction; Structure; Techniques; Testing; Thick; Time; Tissues; age effect; clinically relevant; digital imaging; new technology; optical imaging; pressure; programs; reconstruction; research study; sample fixation; second harmonic; size; success

DESCRIPTION (provided by applicant): Glaucoma represents the second leading cause of blindness worldwide. While both age and intraocular pressure (IOP) are well-recognized risk factors for this disease, the underlying pathologic process involves accelerated death of retinal ganglion cells (RGC) that is associated with progressive loss of vision. For several decades loss of RGCs has been explained primarily by injury to axons in the optic nerve head (ONH) due to the anatomic and mechanical features of the lamina cribrosa, the specialized ONH zone comprised of collagen beams that define the channels or pores through which axon bundles exit the eye. Many studies have examined the effects of IOP on the lamina cribrosa; however, the histologic techniques used involving fixation, embedding and serial sectioning have precluded direct study of IOP effects on collagen beam organization and channel/pore size. The development of confocal microscopy, which optically sections tissue, has provided a new, non-invasive method for dynamically evaluating the 3-dimensional organization of tissue using digital imaging and reconstruction algorithms. Importantly, recent advances in multiphoton confocal microscopy using femtosecond lasers with high-energy pulses that generate second harmonic (SH) signals from collagen allows for direct optical imaging of the lamina cribrosa, non-invasively over time. The application of SH imaging microscopy (SHIM) to the study of the ONH provides for the first time the ability to test the general hypothesis that increasing intraocular pressure in the same eye results in the independent movement of ONH collagen beams leading to distortion of the lamina cribrosa channels and compression of the axon bundles. To test this hypothesis we propose to: 1. Develop an experimental chamber that will allow pressurizing fresh, unfixed human ONH and allow its dynamic examination by SHIM. 2. Determine the effects of changing pressure on lamina cribrosa pore size and shape in individual human ONH as a function of depth and location. We believe that demonstrated success in our ability to visualize the lamina cribrosa using SHIM will strongly support expanded study of the mechanical properties of lamina cribrosa and the consequent effects of age and ethnicity, important predictors of progressive glaucoma damage. Glaucoma causes progressive loss of vision accompanied by changes in the structure of the optic nerve head typically described as increased cupping. Advancing age and increasing eye pressure are risk factors for progression of glaucoma. We propose to use a new technology to visualize the optic nerve head with high resolution and non-invasively. This technique allows for direct measurement of the structural changes in the associated with glaucoma and has direct clinical relevance and application.

描述（由申请人提供）：青光眼是全球第二大致盲原因。虽然年龄和眼压（IOP）都是该病公认的危险因素，但潜在的病理过程涉及视网膜神经节细胞（RGC）的加速死亡，这与进行性视力丧失有关。几十年来，RGCs的丧失主要被解释为视神经头（ONH）轴突的损伤，这是由于网层的解剖和力学特征造成的，网层是一个特殊的视神经头区，由胶原蛋白束组成，这些胶原蛋白束定义了轴突束从眼睛流出的通道或毛孔。许多研究已经检查了眼压对筛板的影响；然而，包括固定、包埋和连续切片在内的组织学技术妨碍了对IOP对胶原束组织和通道/孔隙大小的影响的直接研究。共聚焦显微镜的发展，光学切片组织，提供了一种新的，无创的方法来动态评估组织的三维组织使用数字成像和重建算法。重要的是，多光子共聚焦显微镜的最新进展是使用飞秒激光和高能量脉冲，从胶原蛋白中产生二次谐波（SH）信号，允许对网层进行直接光学成像，无创时间。将SH成像显微镜（SHIM）应用于ONH的研究，首次提供了验证一般假设的能力，即同一只眼睛内眼压升高会导致ONH胶原束的独立运动，从而导致网层通道扭曲和轴突束受压。为了验证这一假设，我们提出：1。开发一个实验室，可以对新鲜的、未固定的人体ONH加压，并允许SHIM对其进行动态检查。2. 确定压力变化对人类ONH个体筛网孔大小和形状的影响，作为深度和位置的函数。我们相信，我们使用SHIM可视化筛板的能力所取得的成功，将有力地支持扩大筛板力学特性的研究，以及年龄和种族的影响，这是进行性青光眼损伤的重要预测因素。青光眼导致视力逐渐丧失，并伴有视神经头部结构的变化，通常描述为拔火罐增加。年龄增长和眼压升高是青光眼发展的危险因素。我们提出了一种高分辨率、无创视神经头可视化的新技术。该技术允许直接测量与青光眼相关的结构变化，具有直接的临床相关性和应用。