青光眼的视神经保护策略

目前对青光眼的治疗方法主要是通过药物或手术降低眼压,然而单纯降低眼压并不足以防止青光眼引起的视神经进行性损害,其他病理机制也很可能导致视网膜神经节细胞(retinal ganglion cell,RGC)和视神经的损伤。所有可能造成RGC凋亡的因素如谷氨酸毒性、营养因子中断、血管异常、胶质细胞活化及一氧化氮的毒性等,均可能与青光眼的病变有关。虽然目前尚无一种被完全公认的青光眼发生机制,     

视神经挫伤后视网膜形态学和Bcl-2/Bax表达

目的 研究大鼠视神经夹挫伤后视网膜神经节细胞（RGC）形态学改变及Bcl-2／Bax蛋白表达的变化，为了解视神经损伤的病理机制提供一定的依据。方法 建立大鼠视神经夹挫伤动物模型，伤后1d、3d、5d、7d、9d、2周、4周处死，HE染色观察RGC的动态变化，免疫组化方法检测RGC表达Bcl-2及Bax的水平。结果 视神经伤后RGC数目严重下降，2周内RGC快速减少，2周以后缓慢减少；伤后Bcl-2及Bax表达随时间而有不同程度的增加，Bax对损伤的反应较Bcl-2稍晚，两者表达均呈现先升后降的趋势，并维持一定的时间。Bcl-2和Bax蛋白表达比与RGC存活数目有一定的相关性。结论 视神经损伤后RGC数目减少是其视功能下降的病理基础之一，Bcl-2和Bax在RGC死亡机制中起重要作用，Bcl-2／Bax比率与RGC的减少呈一定的相关性。     

视盘生物力学的研究进展

生物力学因素与青光眼视神经病变有关,筛板处的缺血和作用于该处的机械压力,在青光眼的轴浆流损害中起着重要作用。根据生物力学的基本原理,分析视盘的几何形状、材料特性、周边环境和机械负荷等生物力学环境,建立计算机辅助的视盘3-维有限元素模型,观察在不同眼压下视盘周围巩膜的结缔组织,筛板前后的神经组织,筛板,巩膜管壁的张力、压力和变形;研究视盘生物力学特点与青光眼视功能丧失的关系,探讨青光眼的病因及不同个体对眼压的易感性。     

青光眼周边部视神经纤维损伤机制探讨

目的:比较正常人和青光眼患者视盘周围巩膜纵切面形态(经过视神经中轴)以及神经纤维变化,结合生物力学原理,探讨青光眼周边部视神经损伤机制。方法:对捐献的12个正常人眼和12个青光眼绝对期患者的视神经及其周围组织标本进行固定、切片、格利染色,比较视盘周围巩膜纵切面(经过视神经中心)形态,观察毗邻的周边部视神经纤维走行特点。结果:视盘周围巩膜孔的纵切面为一锐角(平均角度为73.3°),青光眼绝对期患者残留的视盘周围巩膜纵切面也是锐角(平均角度为75.6°),两者差异无显著性(t=1.44,P>0.05)。正常人视神经纤维从视网膜到筛板的走行变化急剧,青光眼绝对期患者该段视神经纤维消失。结论:视盘周围的巩膜前缘和内侧缘夹角为锐角。青光眼绝对期视神经纤维消失的原因可能与高眼压和视盘周围巩膜的形态、巩膜和视神经纤维的剪切模量、以及"折曲损伤"机制有关。     

青光眼模型视神经损伤的评估方法

对青光眼动物模型视神经损伤的评估有利于青光眼发病机制和治疗方法的研究.目前主要从视网膜神经节细胞(retinal ganglion cell,RGC)计数、视网膜内层厚度测定和球后视神经轴突计数三方面进行评估.几种评估方法各有优缺点.RGC的凋亡直接反映视神经损伤的程度,视网膜全铺片染色计数RGC方法操作较简单,但视网膜铺片各层细胞易于重叠;逆行荧光染料标记需进行颅内手术且染料可能泄露到邻近小胶质细胞,导致不准确的计数;视网膜厚度测量不能直接反映视神经损伤的程度;视神经轴突计数难度相对较高;体视学方法可直接计数RGC,但需要熟悉相关体视学公式及方法,目前在该领域的报道较少.     

内源性视网膜神经节细胞的保护机制

几乎所有视神经病变的最后通路均为视网膜神经节细胞(retinal ganglion cell,RGG)的凋亡.视神经损伤后RGC的凋亡滞后,且在相当长的时间内仍有RGC幸存,说明损伤后RGC凋亡并没有立即启动,可能有其他抵抗因子在发挥作用.因此,研究RGC幸存机制并最终找到视神经保护治疗的新方法具有重要意义.当前,轴突损伤后视神经保护治疗仍以预防RGC凋亡为主,对RGC保护的介绍很少涉及内源性机制,本文主要就内源性RGC的保护机制和一些对视神经有保护作用的内源性因子进行综述.[眼科新进展2009;29(6):468-471]     

青光眼的中枢损伤

青光眼性损伤的形态学特征及病理机制 ,在视网膜节细胞水平及视神经水平已得到广泛研究 ;最近研究表明 ,青光眼对外侧膝状体、视皮质等中枢视路也存在相应损伤 ,并且提示青光眼的中枢损伤可能参与视功能状态的进一步恶化。我们对近年来青光眼中枢损伤的病理形态学及病理机制研究作一综述。     

视网膜神经节细胞的分类和功能研究进展

视网膜神经节细胞(RGC)是视觉通路中最重要的一类神经细胞, 其轴突组成的视神经是视觉信号传递到大脑的唯一通路, 对RGC的形态学特性、基因表达特性、空间分布特性以及功能特性进行研究具有重要意义。本文汇总相关研究进展, 对RGC的分类、目前已明确的RGC类型以及不同损伤下不同类型RGC的损伤特点进行综述, 为全面了解RGC的生理学、病理学特征和视神经损伤相关疾病提供参考。     

玻璃体切割术后继发青光眼的病因及治疗

继发性青光眼（secondary glaucoma,SG）是玻璃体切割术术后的并发症之一,其病因机制繁多。如不及时有效处理,可导致视神经不可逆性损伤、视野缺损,甚至视力丧失。目前此病在国内外比较重视并有一定的报道,本文就玻璃体切割术后继发性青光眼的病因病理机制及治疗手段,进行总结分析如下。     

Alteration in ocular blood flow and its effect on the progression of glaucoma

青光眼是由多种因素引起的神经退行性疾病,眼压过高会损害视神经而导致永久性视力丧失。虽然青光眼的基本病理生理机制尚未确定,但眼组织如视神经,视网膜,脉络膜以及虹膜的血流改变是青光眼发病的重要危险因素。由于不同因素所引发的视神经损害的有限认知,测量方法和治疗方面缺乏,人们对青光眼的理解存在障碍。尽管研究人员在不断地积累证据,力证眼血流的变化在青光眼发病机制中起着重要的作用,但大部分情况下,对于眼血流的变化和青光眼的患病风险之间的关系,他们都持有多样甚至矛盾的结论。本文中,我们回顾了青光眼的不同方面以及眼血流在疾病发展中的影响。     

Biomechanics of the sclera and effects on intraocular pressure

Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells (RGC), resulting in gradual and progressive permanent loss of vision. Reducing intraocular pressure (IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment. However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.     

Scleral structure and biomechanics

As the eye's main load-bearing connective tissue, the sclera is centrally important to vision. In addition to cooperatively maintaining refractive status with the cornea, the sclera must also provide stable mechanical support to vulnerable internal ocular structures such as the retina and optic nerve head. Moreover, it must achieve this under complex, dynamic loading conditions imposed by eye movements and fluid pressures. Recent years have seen significant advances in our knowledge of scleral biomechanics, its modulation with ageing and disease, and their relationship to the hierarchical structure of the collagen-rich scleral extracellular matrix (ECM) and its resident cells. This review focuses on notable recent structural and biomechanical studies, setting their findings in the context of the wider scleral literature. It reviews recent progress in the development of scattering and bioimaging methods to resolve scleral ECM structure at multiple scales. In vivo and ex vivo experimental methods to characterise scleral biomechanics are explored, along with computational techniques that combine structural and biomechanical data to simulate ocular behaviour and extract tissue material properties. Studies into alterations of scleral structure and biomechanics in myopia and glaucoma are presented, and their results reconciled with associated findings on changes in the ageing eye. Finally, new developments in scleral surgery and emerging minimally invasive therapies are highlighted that could offer new hope in the fight against escalating scleral-related vision disorder worldwide.     

Quantitative Mapping of Collagen Fiber Orientation in Non-glaucoma and Glaucoma Posterior Human Sclerae

Purpose. The posterior sclera has a major biomechanical influence on the optic nerve head, and may therefore be important in glaucoma. Scleral material properties are influenced significantly by collagen fiber architecture. Here we quantitatively map fiber orientation in non-glaucoma and glaucoma posterior human sclerae. Methods. Wide-angle x-ray scattering quantified fiber orientation at 0.5-mm intervals across seven non-glaucoma post-mortem human sclerae, and five sclerae with glaucoma history and confirmed axon loss. Multiphoton microscopy provided semiquantitative depth-profiling in the peripapillary sclera. Results. Midposterior fiber orientation was either uniaxial (one preferred direction) or biaxial (two directions). The peripapillary sclera was characterized by a ring of fibers located mainly in the mid-/outer stromal depth and encompassing ～50% of the total tissue thickness. Fiber anisotropy was 37% higher in the peripapillary sclera compared with midposterior, varied up to 4-fold with position around the scleral canal, and was consistently lowest in the superior-nasal quadrant. Mean fiber anisotropy was significantly lower in the superior-temporal (P < 0.01) and inferior-nasal (P < 0.05) peripapillary scleral quadrants in glaucoma compared with non-glaucoma eyes. Conclusions. The collagen fiber architecture of the posterior human sclera is highly anisotropic and inhomogeneous. Regional differences in peripapillary fiber anisotropy between non-glaucoma and glaucoma eyes may represent adaptive changes in response to elevated IOP and/or glaucoma, or baseline structural properties that associate with predisposition to glaucomatous axon damage. Quantitative fiber orientation data will benefit numerical eye models aimed at predicting the sclera's influence on nerve head biomechanics, and thereby its possible role in glaucoma.     

Factors influencing optic nerve head biomechanics

PURPOSE: The biomechanical environment within the optic nerve head (ONH) may play a role in retinal ganglion cell loss in glaucomatous optic neuropathy. This was a systematic analysis in which finite element methods were used to determine which anatomic and biomechanical factors most influenced the biomechanical response of the ONH to acute changes in IOP. METHODS: Based on a previously described computational model of the eye, each of 21 input factors, representing the biomechanical properties of relevant ocular tissues, the IOP, and 14 geometric factors were independently varied. The biomechanical response of the ONH tissues was quantified through a set of 29 outcome measures, including peak and mean stress and strain within each tissue, and measures of geometric changes in ONH tissues. Input factors were ranked according to their aggregated influence on groups of outcome measures. RESULTS: The five input factors that had the largest influence across all outcome measures were, in ranked order: stiffness of the sclera, radius of the eye, stiffness of the lamina cribrosa, IOP, and thickness of the scleral shell. The five least influential factors were, in reverse ranked order: retinal thickness, peripapillary rim height, cup depth, cup-to-disc ratio, and pial thickness. Factor ranks were similar for various outcome measure groups and factor ranges. CONCLUSIONS: The model predicts that ONH biomechanics are strongly dependent on scleral biomechanical properties. Acute deformations of ONH tissues, and the consequent high levels of neural tissue strain, were less strongly dependent on the action of IOP directly on the internal surface of the ONH than on the indirect effects of IOP on the sclera. This suggests that interindividual variations in scleral properties could be a risk factor for the development of glaucoma. Eye size and lamina cribrosa biomechanical properties also have a strong influence on ONH biomechanics.     

Structural and ultrastructural changes to the sclera in a mammalian model of high myopia

PURPOSE: The development of high myopia is associated with scleral thinning and changes in the diameter of scleral collagen fibrils in humans. In the present study, the association between these scleral changes and the losses in scleral tissue that have previously been reported in animal models were investigated to determine the relationship between changes in collagen fibril architecture and thinning of the sclera in high myopia. METHODS: Myopia was induced in young tree shrews by monocular deprivation of pattern vision for short-term (12 days) or long-term (3-20 months) periods. Scleral tissue from normal animals over a wide age range (birth to 21 months) was also collected to provide data on the normal development of the sclera. Light and electron microscopy were used to measure scleral thickness and to determine the frequency distribution of collagen fibril diameters in the sclera. Tissue loss was monitored through measures of scleral dry weight. RESULTS: Significant scleral thinning and tissue loss, particularly at the posterior pole of the eye, were associated with ocular enlargement and myopia development after both short- and long-term treatments. However, collagen fibril diameter distribution was not significantly altered after short-term myopia treatment, whereas, from 3 months of monocular deprivation onward, significant reductions in the median collagen fibril diameter were noted, particularly at the posterior pole. CONCLUSIONS: The results of this study demonstrated that loss of scleral tissue and subsequent scleral thinning occurred rapidly during development of axial myopia. However, this initial tissue loss progressed in a way that did not result in significant alterations to the collagen fibril diameter distribution. In the longer term, there was an increased number of small diameter collagen fibrils in the sclera of highly myopic eyes, which is consistent with findings in humans and is likely to contribute to the weakened biomechanical properties of the sclera that have previously been reported.     

Regional optic nerve damage in experimental mouse glaucoma

PURPOSE: To assess the relationship between regional variation of axon loss and optic nerve head anatomy in laser-induced experimental glaucoma in the mouse. METHODS: Experimental glaucoma was induced unilaterally in eight NIH Swiss black mice. Intraocular pressure (IOP) was measured for 12 weeks, and the mice were killed. The eyes were enucleated, and both optic nerves were dissected and processed conventionally for electron microscopy. Low- and high-magnification images of the optic nerve cross sections 300 microm posterior to the globe were collected systematically and masked before analysis. For each nerve, cross-sectional area was measured in low-magnification micrographs. Axon number and density were determined in the high-magnification micrographs. Loss of axonal density was compared between the superior and inferior and nasal and temporal areas of the optic nerve cross section. Additional cross-section micrographs were collected at 10- or 20-microm intervals throughout the optic nerve head. RESULTS: In the treated (glaucoma) eyes, mean IOP was 44% higher than that in the control eyes. The optic nerve cross-sectional area, mean axonal density, and total axonal number were significantly less than those in the control eyes (P < 0.01 for each). Axon loss in the superior optic nerve was greater than in the inferior optic nerve in each glaucomatous eye (P = 0.012). The ratio of axonal density in the superior and inferior optic nerve (superior-to-inferior [S/I] ratio) in all treated eyes was <1.0 and significantly lower than that in the control eyes (P = 0.012). The central retinal vessels occupied approximately 20% of the central optic nerve head cross-sectional area, gradually shifted position ventrally as they progressed toward the scleral foramen (the mouse does not have a lamina cribrosa), and exited the inferior retrobulbar optic nerve adjacent to the posterior of the globe. CONCLUSIONS: Ocular hypertension in the mouse eye sufficient to cause optic nerve damage induces preferential loss of superior optic nerve axons. Optic nerve axon loss appeared less among the axons that were near the major optic nerve blood vessels at the scleral foramen. Topographic differences in optic nerve axon loss should be considered when evaluating optic nerve damage in experimental laser-induced glaucoma in the mouse.     

Correlation of the blind spot size to the area of the optic disk and parapapillary atrophy

We evaluated the relationship between the optic disk and the blind spot area. Using kinetic Goldmann perimetry in 23 patients with open-angle glaucoma and 19 normal subjects, the blind spot size was correlated significantly with the total area of the optic disk, peripapillary scleral ring, and parapapillary chorioretinal atrophy. Zone beta of the parapapillary atrophy with a visible sclera was attributed to an absolute scotoma, and zone alpha with irregular pigmentation was attributed to a relative scotoma. The blind spot was significantly larger in the glaucomatous eyes than in the normal eyes, which corresponded with a larger zone beta in the glaucomatous eyes. The intrapapillary and parapapillary region of the optic nerve head correlated to the size of the blind spot, which included the parapapillary chorioretinal atrophy and a significant size difference between normal and glaucomatous eyes.     

角膜滞后量在青光眼中的作用

青光眼是全球首位不可逆致盲性眼病,其具体发病机制尚不清楚,但颇受重视的是眼压和房水流出通道等方面。近年,研究人员开始越来越多地关注非压力依赖因素如角膜滞后量(CH)在青光眼中的作用。CH是角膜的生物力学参数,它反映了角膜的黏性阻力,即吸收和分散能量的能力。CH在临床上很容易获得,可作为眼后部组织生物力学特性的替代标志物,如筛板和乳头周围巩膜,这些组织可能与青光眼损伤的易感性有关。有研究提供了CH与青光眼临床相关结果之间的联系的证据。本文综述了CH在青光眼中的作用的最新发现,从CH的测量方法、CH与中央角膜厚度、青光眼性视野进展、视盘损害、视网膜神经纤维层缺失等方面进行了归纳和总结。     

Thickness of the lamina cribrosa and peripapillary sclera in Rhesus monkeys with nonglaucomatous or glaucomatous optic neuropathy

Purpose: To measure the thickness of the lamina cribrosa and peripapillary sclera in monkeys with a nonglaucomatous optic nerve damage and to compare that with those of monkeys with glaucomatous optic neuropathy. Methods: The study included 22 monkey eyes (Macaca mulatta) which had undergone a temporary experimental central retinal artery occlusion (CRAO) and seven monkey eyes in which experimental glaucoma was unilaterally produced. We measured histomorphometrically the thickness of the lamina cribrosa and peripapillary sclera. Results: The lamina cribrosa was significantly thicker in the CRAO group than in the glaucoma group (central region: 212 ± 46 μm versus 167 ± 17 μm; p = 0.009). The thickness of the peripapillary sclera at the optic disc border (253 ± 39 μm versus 192 ± 21 μm; p = 0.001) and outside of the optic nerve meninges (408 ± 70 μm versus 314 ± 64 μm; p = 0.006) was significantly greater in the CRAO group. Conclusions: In monkey eyes with a temporary CRAO as a model for nonglaucomatous optic nerve damage, the lamina cribrosa is significantly thicker than in monkey eyes with experimental glaucomatous optic nerve damage. It may suggest that the loss of optic nerve fibres might not be the reason for the thinning of the lamina cribrosa in eyes with advanced glaucoma. The thinner peripapillary sclera in the glaucomatous eyes may suggest that the monkey sclera is more vulnerable to stretching with increased intraocular pressure than the human eye for which no glaucoma‐related lengthening of the eyeball and thinning of the peripapillary sclera have been observed.