Pressure Induced Dynamic 3D Changes in Lamina Cribrosa

描述（由申请人提供）：青光眼是全球第二大致盲原因。虽然年龄和眼内压（IOP）都是这种疾病的公认风险因素，但潜在的病理过程涉及视网膜神经节细胞（RGC）的加速死亡，这与视力的进行性丧失有关。几十年来，RGC的损失主要被解释为由于筛板的解剖和机械特征而导致的视神经头（ONH）中轴突的损伤，筛板是由胶原束组成的专门的ONH区，胶原束限定轴突束通过其离开眼睛的通道或孔。许多研究已经检查了IOP对筛板的影响;然而，所使用的组织学技术包括固定、包埋和连续切片，无法直接研究IOP对胶原束组织和通道/孔径的影响。光学切片组织的共聚焦显微镜的发展，提供了一种新的，非侵入性的方法，动态评估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，使用飞秒激光与高能量脉冲，从胶原蛋白产生二次谐波（SH）信号，允许直接光学成像的筛板，非侵入性的随着时间的推移。SH成像显微镜（SHIM）的研究ONH的应用提供了第一次的能力，以测试一般假设，增加眼内压在同一只眼睛的结果在独立的运动ONH胶原光束导致筛板通道的扭曲和压缩的轴突束。为了验证这一假设，我们建议：1。开发一个实验室，将允许加压新鲜，未固定的人ONH，并允许其动态检查SHIM。2.确定压力变化对个体人类ONH中筛板孔径和形状的影响，作为深度和位置的函数。我们相信，成功地证明了我们的能力，可视化筛板使用SHIM将有力地支持扩大研究的机械性能的筛板和随之而来的影响，年龄和种族，进行性青光眼损害的重要预测因素。青光眼引起视力的进行性丧失，伴随着视神经乳头结构的变化，通常被描述为增加的杯状突起。年龄增长和眼压升高是青光眼进展的危险因素。我们建议使用一种新的技术来可视化的视神经乳头与高分辨率和非侵入性。该技术允许直接测量与青光眼相关的结构变化，并具有直接的临床相关性和应用。

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.