小胶质细胞极化在青光眼视神经损伤发病机制及治疗中的研究进展

青光眼是多因素介导的以视网膜神经节细胞凋亡、视神经萎缩和视野缺损为特征的神经退行性眼病,发病机制尚不明确.小胶质细胞是视网膜内常驻的免疫细胞,它可分为经典激活M1型和替代激活M2型,随着眼压改变以及视网膜神经节细胞损伤修复过程的进展,小胶质细胞的极性呈现动态变化,可产生多种具有神经毒性或神经保护作用的细胞因子.近年来,...     

青光眼视神经损伤进展的视盘形态学危险因素

本从C／D值、盘沿面积、盘周萎缩区、视网膜血管直径以及视盘出血等方面综述了青光眼视神经损伤进展的视盘形态学危险因素。     

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。     

原发性开角型青光眼视神经损伤不同阶段血清细胞因子水平分析及临床意义

目的：探讨原发性开角型青光眼（ POAG）视神经损伤不同阶段患者血清中各细胞因子的水平,并分析其临床意义。方法选择2012年8月至2014年8月在我院接受治疗的POAG患者97例（172只眼）,作为观察组。再选择同期在我院眼科接受治疗的白内障患者50例,作为对照组。对比两组眼压及视力情况,对相关细胞因子水平进行对比分析。然后根据MD值分组得到A、B、C组,并对比三组间的眼压、视力、细胞因子水平等。结果观察组眼压、近视患者所占比例以及白细胞介素-4（ IL-4）水平显著高于对照组,而IL-6及IL-12水平低于对照组。观察组中根据不同视神经损伤程度分为A、B、C组发现A、B、C组眼压呈上升趋势,并且三组间眼压显著差异。并且A组近视比例低于C组,A组、B组IL-12水平显著高于C组,差异均有统计学意义（均P ＜0．05）。其他水平不存在显著差异（ P ＞0．05）。结论 POAG出现眼压升高、视力下降的可能性增大,其中IL-4会对视神经造成一定程度的损伤,相反IL-6以及L-12具有保护作用。此外,在POAG视神经不同损伤阶段仅有IL-12水平波动显著,说明相关的免疫应答反应在视神经损伤过程中的作用显著。     

青光眼视杯逆转的研究进展

先天性青光眼当其眼压获得有效控制时，青光眼视杯可出现可逆性改变。但成年青光眼视杯治疗能否使其逆转目前尚无定论。近年来随着计算机图像分析技术在青光眼诊断中的成功应用，使视乳头测量的精确度大大提高，为青光眼视杯逆转研究提供了客观的先进手段。     

眼底图像配准检测青光眼视神经损伤变化

眼底图像配准是将间隔一段时间拍摄的眼底图像,通过软件搜索特征后进行叠加和重合并交替闪烁显示,以便观察者可清晰观察到眼底图像因时间不同出现的细微变化。《中国青光眼指南（2020年）》已将眼底图像配准列为观察青光眼眼底解剖结构改变和损伤进展的推荐使用方法。本文从视神经形态随访检查方法的优劣和眼底图像配准检测青光眼视神经损伤...     

Nogo在视神经损伤后再生中的研究进展

哺乳动物外周神经损伤后轴突能再生很长距离。在一定条件下,中枢神经系统受损后也能部分再生。Nogo是一种已经被证实的髓鞘相关抑制因子,中枢神经损伤后Nogo释放增加、表达增强,启动神经元凋亡过程,导致神经元死亡。我们从Nogo-A,Nogo-66,可溶性NgR片段、RhoA酶与Rho-A/Rho激酶信号通道、钙离子几个方面综述Nogo的作用机制,并探讨其在视神经损伤后神经再生中的应用前景。     

视神经损伤及其再生

视神经损伤的病理过程复杂,再生过程受诸多因素影响,近10年已从其解剖、生理、生物化学方面进行了较多研究,并已得到一些明确的结论。促进视神经再生的问题不再是可望而不可及的了,随着研究的深入,一些研究成果将会应用到人视神经损伤疾病的治疗中.（中华眼底病杂志,2000,16：71-138）     

急性视神经损伤25例报告

本文总结25例视神经损伤。锐器占12％,视神经骨管部损伤占88％,青壮年19～30岁占50％。多合并颅骨、眶骨、颧骨多发性骨折及脑组织严重损伤及视力严重损害;无光感6例占24％,光感到手动12例占48％。临床实践证明,药物保守疗法难以奏效,预防工作至关重要。     

原发性急性闭角型青光眼患者视神经的评估

目的:检测原发性急性闭角型青光眼患者视神经的形态及功能变化来评估视神经的损害情况。方法:对28例原发性急性闭角型青光眼患者行眼底照像、视野、视神经OCT扫描、图形视觉诱发电位等检查结果阳性率进行分析。结果:患者28例28眼中,能获取视神经图像25眼(89%),25眼中视盘颜色：正常9眼,充血水肿16眼,未出现苍白;C/D:<0.6者5眼,>0.6者1眼,不能分辨的有19眼;盘沿情况：正常6眼,不能分辨的有19眼;无法获取视神经图像3眼(11%)。视野检查：正常9眼(32%),出现视野损害的2眼(7%),因白内障视野检测无参考意义8眼(29%),假阳性率≥15%的2眼(7%),不能配合检查7眼(25%)。OCT视盘周围视网膜神经纤维层厚度检查：能测量的26眼(93%),其中神经纤维层厚度正常24眼,神经纤维层厚度局部变薄2眼。屈光间质严重混浊不能测量2眼(7%);P-VEP检查中P100波峰时正常的18眼(64%),峰时延长的10眼(36%)。P100波振幅正常的11眼(39%),振幅降低的17眼(61%)。结论:原发性急性闭角型青光眼急性大发作后视神经并不出现典型的青光眼损...     

青光眼视神经保护治疗的研究进展

青光眼是由于眼压升高引起视乳头损害和视野缺损的一种致盲性眼病,其病理基础是视网膜神经节细胞及其轴突的进行性丢失。过去大量的研究都集中在降低眼压方面,现在视神经保护治疗作为一种通过阻止神经元死亡治疗青光眼的新策略已被普遍接受。我们从NMDA受体拮抗剂、神经营养因子、热休克蛋白、免疫系统等方面,总结了目前青光眼视神经保护治疗的研究进展。     

Association between corneal biomechanical properties and optic nerve head morphology in newly diagnosed glaucoma patients

Background: To investigate the association between corneal biomechanics and optic nerve head morphology in newly diagnosed primary open‐angle glaucoma patients. Design: Hospital based prospective study. Participants: Forty‐two untreated newly diagnosed primary open‐angle glaucoma patients. Methods: Patients underwent corneal hysteresis measurement using the Ocular Response Analyzer and confocal scanning laser ophthalmoscopy for optic nerve head topography evaluation. One eye was selected randomly for analysis. Data collected included age, race, gender, intraocular pressure and central corneal thickness. Main Outcome Measures: Multiple regression analysis (controlling for baseline intraocular pressure and disc area) was used to investigate factors associated with the following optic nerve head topographic parameters: linear cup‐to‐disc ratio and mean cup depth. Results: Mean age of participants was 66.7 ± 11.8 years. Corneal hysteresis was the only factor significantly associated with both mean cup depth (correlation coefficient [r] = ?0.34, P = 0.03) and cup‐to‐disc ratio (r = ?0.41, P = 0.01). Central corneal thickness was significantly associated with mean cup depth (r = ?0.35, P = 0.02), but not with cup‐to‐disc ratio (r = ?0.25, P = 0.13). Although a trend towards a positive association between age and cup‐to‐disc ratio was identified (r = 0.26, P = 0.08), age was not significantly associated with mean cup depth (r = 0.06, P = 0.72). When comparing fellow eyes of patients with bilateral glaucoma, the eye with higher corneal hysteresis had smaller cup‐to‐disc ratio in 75% of the cases. Conclusions: In untreated newly diagnosed primary open‐angle glaucoma patients, those with thinner corneas and mainly lower corneal hysteresis values had a larger cup‐to‐disc ratio and deeper cup, independently of intraocular pressure values and disc size.     

Pathophysiology of human glaucomatous optic nerve damage: Insights from rodent models of glaucoma

Understanding mechanisms of glaucomatous optic nerve damage is essential for developing effective therapies to augment conventional pressure-lowering treatments. This requires that we understand not only the physical forces in play, but the cellular responses that translate these forces into axonal injury. The former are best understood by using primate models, in which a well-developed lamina cribrosa, peripapillary sclera and blood supply are most like that of the human optic nerve head. However, determining cellular responses to elevated intraocular pressure (IOP) and relating their contribution to axonal injury require cell biology techniques, using animals in numbers sufficient to perform reliable statistical analyses and draw meaningful conclusions. Over the years, models of chronically elevated IOP in laboratory rats and mice have proven increasingly useful for these purposes. While lacking a distinct collagenous lamina cribrosa, the rodent optic nerve head (ONH) possesses a cellular arrangement of astrocytes, or glial lamina, that ultrastructurally closely resembles that of the primate. Using these tools, major insights have been gained into ONH and the retinal cellular responses to elevated IOP that, in time, can be applied to the primate model and, ultimately, human glaucoma.     

Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients

Purpose

To investigate factors associated with changes in optic nerve head (ONH) topography after acute intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG).

Methods

Untreated POAG patients (IOP >21 mm Hg) were prospectively enrolled. Systemic and ocular information were collected, including central corneal thickness (CCT) and corneal hysteresis (CH). All patients underwent confocal scanning laser ophthalmoscopy and tonometry (Goldmann) before and 1 h after pharmacological IOP reduction. The mean of three measurements was considered for analysis. Changes in each ONH topographic parameter were assessed (one eye was randomly selected), and those that changed significantly were correlated with patient''s systemic and ocular characteristics.

Results

A total of 42 patients were included (mean age, 66.7±11.8 years). After a mean IOP reduction of 47.3±11.9%, significant changes were observed in cup area and volume, and in rim area and volume (P<0.01), but not in mean cup depth (P=0.80). Multiple regression analysis (controlling for baseline IOP and magnitude of IOP reduction) showed that CH (r²=0.17, P<0.01) and diabetes diagnosis (r²⩾0.21, P<0.01) were negatively correlated with the magnitude of changes in ONH parameters, whereas the cup-to-disc ratio was positively correlated (r²=0.30, P<0.01). Age, race, disc area, and CCT were not significant (P⩾0.12). Including all significant factors in a multivariable model, only the presence of diabetes remained significantly associated with all ONH parameters evaluated (P<0.01).

Conclusions

Different systemic and ocular factors, such as diabetes, CH, and the relative size of the cup, seem to be associated with the magnitude of changes in ONH topography after acute IOP reduction in POAG patients. These associations partially explain the ONH changes observed in these patients and suggest that other factors are possibly implicated in an individual susceptibility to IOP.     

TLR4在青光眼视神经损伤机制中的作用

青光眼是一种以视乳头萎缩凹陷、视野缺损及视力下降为共同特征的不可逆的致盲性疾病,其视神经损伤的本质为视神经节细胞的凋亡。尽管通过药物干预和手术控制眼压可以对青光眼起到一定的治疗作用,但如何从根本上阻止青光眼的进一步发展仍处于探索阶段。因此,研究青光眼视神经损伤机制,通过阻断视神经损伤而治疗青光眼至关重要。近几年,免疫机制对青光眼视神经损伤的影响成为研究热点,本文中主要对Toll样受体4(TLR4)通过不同免疫通路并与神经胶质细胞相互作用引起青光眼患者视神经损伤进行综述。     

原发性青光眼视神经损害的发生机制

关于原发性青光眼的发病机制,目前有许多学说,但每种学说都不能完全说明青光眼视神经损害的具体机制。综合分析发现,每个正常人或青光眼患者身上都具有致视神经损害因素和抗视神经损害因素,青光眼发生与否是这两种因素相斗争的结果。眼压虽然不是青光眼视神经损害的唯一因素,但仍然是青光眼最主要和最稳定的危险因素。另外,血循环因素和免疫因素也是导致青光眼视神经损害的重要原因。本文综合分析了近年来有关原发性青光眼视神经损害机制的研究,并以独特的视角分析了眼压对青光眼视神经损害的具体机制。     

Finite element modeling of the human sclera: influence on optic nerve head biomechanics and connections with glaucoma

Scleral thickness, especially near the optic nerve head (ONH), is a potential factor of interest in the development of glaucomatous optic neuropathy. Large differences in the dimensions of the sclera, the principal load-bearing tissue of the eye, have been observed between individuals. This study aimed to characterize the effects of these differences on ONH biomechanics. Eleven enucleated human globes (7 normal and 4 ostensibly glaucomatous) were imaged using high-field microMRI and segmented to produce 3-D individual-specific corneoscleral shells. An identical, idealized ONH geometry was inserted into each shell. Finite element modeling predicted the effects of pressurizing the eyes to an IOP of 30 mmHg, with the results used to characterize the effect of inter-individual differences in scleral dimensions on the biomechanics of the ONH. Measurements of the individual-specific corneoscleral shells were used to construct a 2-D axisymmetric idealized model of the corneoscleral shell and ONH. A sensitivity analysis based on this model quantified the relative importance of different geometrical characteristics of the scleral shell on the biomechanics of the ONH. Significant variations were observed in various measures of strain in the idealized lamina cribrosa (LC) across the seven normal corneoscleral shells, implying large differences in individual biomechanics due to scleral anatomy variations alone. The sensitivity analysis revealed that scleral thickness adjacent to the ONH was responsible for the vast majority of variation. Remarkably, varying peripapilary scleral thickness over the physiologically measured range changed the peak (95th percentile) first principal strain in the LC and radial displacement of the ONH canal by an amount that was equivalent to a change in IOP of 15 mmHg. Inter-individual variations in scleral thickness, particularly peripapillary scleral thickness, can result in vastly different biomechanical responses to IOP. These differences may be significant for understanding the interactions between IOP and scleral biomechanics in the pathogenesis of glaucomatous optic neuropathy. The relationship between scleral thickness and material properties needs to be studied in human eyes.     

Histomorphometric measurements in human and dog optic nerve and an estimation of optic nerve pressure gradients in human

Intraocular pressure and cerebrospinal fluid (CSF) pressure are important determinants of the trans-laminar pressure gradient which is believed to be important in the pathogenesis of glaucomatous optic nerve degeneration. Computational models and finite element calculations of optic nerve head biomechanics have been previously used to predict pressures and stresses in the human optic nerve. The purpose of this report is to morphometrically compare the optic nerve laminar and pia mater structure between humans and dogs, and to use previously reported tissue pressure measurements in the dog optic nerve to estimate individual-specific human optic nerve pressures and pressure gradients. High resolution light microscopy was used to acquire quantitative histological measurements from sagittal sections taken from the middle of the optic nerve in 34 human cadaveric eyes and 10 dog eyes. Parameters measured included the pre-laminar and lamina cribrosa thickness, distance from posterior boundary of lamina cribrosa to inner limiting membrane (ILM), shortest distance between anterior lamina cribrosa surface and subarachnoid space, shortest distance between ILM and inner surface of pia mater in contact with the subarachnoid space and optic nerve diameter. Pia mater thickness in the proximal 4 mm of post-laminar nerve was also determined. There was no significant difference in lamina cribrosa thickness between dog and human eyes (P = 0.356). The distance between the intraocular and subarachnoid space was greater in dogs (P < 0.001). Pia mater thickness was greatest at the termination of subarachnoid space in both species. In humans, pia mater thickness decreased over the proximal 500 μm to reach a constant value of approximately 60 μm. In dogs this decrease occurred over 1000 μm to reach a constant diameter of approximately 30 μm. Using previous measurements of optic nerve pressures and pressure gradients in dogs we estimate that at an IOP of 15 mmHg and a CSF pressure of 0 mmHg the mean pressure difference across the human pia mater will be 4.8 ± 2.2 mmHg. If we assume that the pressure difference between the intraocular space and post-laminar tissue falls across the entire thickness of the human lamina cribrosa then an estimate of the trans-laminar pressure gradient is 2.0 ± 0.8 mmHg/100 μm. If we assume that this pressure difference only occurs across the dense collagenous plates of the posterior lamina cribrosa then a trans-laminar pressure gradient high estimate of 3.3 ± 1.4 mmHg/100 μm is calculated. Changes in tissue pressure gradients in the optic nerve may be an important factor in the pathogenesis of glaucomatous optic neuropathy.     

Research progress of stem cells on glaucomatous optic nerve injury

Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.