鼠青光眼模型的眼压测量方法

青光眼是主要的致盲眼病之一,对于该病病因、病理、预防、诊断和治疗的研究都需要青光眼动物模型。近年青光眼鼠模型应用报道越来越多。但由于鼠眼较小,对其眼压测量有一定特殊性,我们对鼠青光眼模型的眼压测量方法,尤其是各种方法的原理、特点进行综述。     

复方卡波姆诱发的兔高眼压模型与其它兔高眼压模型的比较研究

目的 建立适用于研究抗青光眼药物降眼压作用及保护视神经作用的兔青光眼模型。方法 将21只兔随机分为I、Ⅱ、Ⅲ及Ⅳ组,分别对其前房内注射复方卡波姆、甲基纤维素及复方甲基纤维素,结膜下注射地塞米松诱发青光眼,并对4种药物诱发的青光眼模型进行观察。结果 I组高眼压持续20－50d,平均眼压为29－35mmHg(1mmHg=0.133kPa),眼压峰值为37－45mmHg,青光眼模型成功率为91．7％。Ⅱ及Ⅲ级模型有10－20％的兔眼眼压升主持续3－4d,如按眼压为22mmHg持续1周的标准判断,Ⅱ及Ⅲ组模型均不理想。Ⅳ组眼压平均升高3mmHg,持续7d,亦为失败模型。结论 复方卡波姆诱发的兔青光眼模型具有引起眼压中度、稳定升高的时间长,方法简单,易于操作和控制等优点。可用于对青光眼性视神经视网膜损害的研究及对抗青光眼药物的研究,是一种较理想的兔青光眼模型。     

鼠青光眼模型中热休克蛋白27的表达及其作用

目的:探讨热休克蛋白27(HSP27)在鼠青光眼模型视网膜神经节细胞(RGCs)中的表达以及眼压对抗HSP27自身抗体的影响。方法:使用SPSS12.0软件将55只Wistar大鼠随机分为高眼压组(25只鼠)、sham对照(假手术)组(25只鼠)及正常对照组(5只鼠)。采用电凝鼠巩膜表面至少3组静脉及角膜缘周围血管,建立鼠青光眼模型。采用免疫组化和酶联免疫吸附测定(ELISA)方法分别检测术后1,2,3,4及8wk视网膜中RGCs以及神经纤维层(RNFL)HSP27的表达、分布以及血清中抗HSP27抗体水平。结果:随着眼压升高及高眼压持续时间延长,高眼压组右眼RGCs中HSP27表达逐渐增强,与其左眼、sham对照组右、左眼和正常对照组右、左眼比较,差异均有统计学意义(P<0.001),且RNFL中也出现HSP27的表达。高眼压组血清中抗HSP27抗体水平在术后1wk轻度升高(P>0.05),随着眼压升高及高眼压持续至术后8wk,血清中HSP27抗体水平逐渐升高并稳定于较高水平,与sham对照组和正常对照组比较,差异有统计学意义(P<0.05)。结论:内源性HSP27表达增强可能在青光眼视神经病变中具有重要作用。     

高眼压性青光眼动物模型

青光眼是一类非常复杂的眼病,高眼压是青光眼发生,发展的重要因素。本文就高眼压性青光眼模型,尤其是各种实验性青光眼的特点、诱导方法及结果进行综述,并介绍根据不同的研究目的,如何选用合适的模型     

高眼压的处理

“高眼压”是指眼压升高超过正常或平均值而没有视野和视盘的损害。Grant和chandler称之为“无损害的原发性开角青光眼”,也有称“疑似青光眼”或“前期青光眼”者。高眼压涉及40岁以上人群的6-10%。而有视神经和视野损害的青光眼仅占0.3-0.5%。正常人平均眼压为15±3mmHg,未经治疗的青光眼病人平均眼压为24±5mmHg。正常人、高眼压和青光眼的眼压存在交叉重迭的情况。用“高眼压”而不用“青光眼”一词,可以避免引起许多潜在问题。对眼压增高而无症状的病人首先要进行全面的检查,包括病史、屈光、裂隙灯检查、压平眼压计测量眼压、眼底检查、视盘照相、前房角镜及视野检查,作出最初的判断:是高眼压还是青光眼,是否应着手治疗?如眼压高于20mmHg,视盘和视野正常,则初诊为“高眼压”,要作定期检查。     

高眼压性青光眼压动物模型

青光眼是一类非常复杂的眼病，高眼压是青光眼发生，发展的重要因素，本文就高眼压性青光眼模型，尤其是各种实验性青光眼的特点，诱导方法及结果进行综述，并介绍根据不同的研究目的，如何选用合适的模型。     

鼠诱发性高眼压和细胞凋亡的实验研究

目的 探讨鼠实验性急慢性高眼压的视网膜组织损伤机制。方法 应用前房内连续灌注生理盐水的方法制成急性高眼压鼠模型。实验后第1、2、4、5、7和10d观察视网膜反应。巩膜表浅静脉烧灼法制成慢性高眼压模型，分别于实验后1和2个月观察视网膜损害情况。用TUNEL技术和半胱胺酸天冬胺酸酶免疫组化研究法以证实视网膜细胞的凋亡机制，NADPH辅酶反应识别一氧化氮诱导的细胞。结果 急性高眼压模型的免疫组化研究证实节细胞凋亡是早期的细胞死亡，而在对照组一氧化氮合成酶在视网膜组织并不表现明显的活性。慢性高眼压模型实验提示一氧化氮合成酶活性增加，表明一氧化氮具有神经保护作用而并非仅存有细胞毒性作用。TUNEL和半胱胺酸天冬胺酸酶研究表明，凋亡开始于慢性高眼压的不同阶段。结论 了解高眼压所致的视网膜损害的机制为研究在细胞变性过程中某些物质对凋亡、一氧化氮合成酶和突触传递的影响，尤其是对研究青光眼节细胞死亡的机制提供了基础。     

中国高眼压症诊断治疗和随访专家共识(2020年)

眼压升高是青光眼进展的主要危险因素,但高眼压并不等同于青光眼,仅眼压高而不合并青光眼为高眼压症。为了降低疾病进展的风险,为我国高眼压症的诊断及治疗规范化、科学化提供参考,中华医学会眼科学分会青光眼学组针对高眼压症的甄别诊断、识别高风险者、个体化预防性治疗和监测等提出共识性意见和建议。     

鼠类慢性高眼压模型的研究进展

青光眼的特征性病变为神经节细胞死亡、视神经变性、视乳头凹陷及进行性的视野缺损.高眼压是青光眼最主要的危险因素之一,因此,国内外的研究者通过建立高眼压动物模型,模拟人类青光眼的主要病理过程,以揭示其发病机制并寻求新的治疗方法.笔者就目前国外研究者对鼠类慢性高眼压模型的建立、模型的评估及模型的应用进行综述,以与眼科同道交流.(中华眼科杂志,2009,45:663-668)     

血压与眼压联合诱发青光眼的生物力学机制

长期以来,人们对于青光眼发病机制的研究大都局限于眼压方面,而对可能参与诱发青光眼的其它因素则很少进行探讨。但是,依照目前单纯考虑眼压因素的观点很难解释低眼压性青光眼或“良性高眼压症”等的客观存在,这就暴露出现有青光眼病因学说的缺陷。本文乃是从生物力学角度探讨青光眼病因机制的一次尝试。文中从维持眼球正常血液循环的必要条件出发,建立了综合考虑眼压与血压两种因素的青光眼病理指标,(经与122例240只眼的临床诊断结论对照,符合率为97%。一、文献复习及问题的提出青光眼是一种古老而常见的眼科疾患,阿     

Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma

The pathogenesis of normal (intraocular) pressure glaucoma has remained unclear so far. As hospital‐based studies showed an association of normal‐pressure glaucoma with low systemic blood pressure, particularly at night, and with vasospastic symptoms, it has been hypothesized that a vascular factor may play a primary role in the pathogenesis of normal‐pressure glaucoma. That assumption may, however, be contradicted by the morphology of the optic nerve head. Eyes with normal‐pressure glaucoma and glaucomatous eyes with high‐intraocular pressure can show a strikingly similar appearance of the optic nerve head, including a loss of neuroretinal rim, a deepening of the optic cup, and an enlargement of parapapillary atrophy. These features, however, are not found in any (other) vascular optic neuropathy, with the exception of an enlargement and deepening of the optic cup in arteritic anterior ischaemic optic neuropathy. One may additionally take into account (i) that it is the trans‐lamina cribrosa pressure difference (and not the trans‐corneal pressure difference, i.e. the so‐called intraocular pressure) which is of importance for the physiology and pathophysiology of the optic nerve head; (ii) that studies have shown that the anatomy of the optic nerve head including the intraocular pressure, the anatomy and biomechanics of the lamina cribrosa and peripapillary sclera, retrobulbar orbital cerebrospinal fluid pressure and the retrobulbar optic nerve tissue pressure may be of importance for the pathogenesis of the highly myopic type of chronic open‐angle glaucoma; (iii) that studies have suggested a physiological association between the pressure in all three fluid filled compartments, i.e. the systemic arterial blood pressure, the cerebrospinal fluid pressure and the intraocular pressure; (iv) that an experimental investigation suggested that a low cerebrospinal fluid pressure may play a role in the pathogenesis of normal (intraocular) pressure glaucoma; and (v) that recent clinical studies reported that patients with normal (intraocular) pressure glaucoma had significantly lower cerebrospinal fluid pressure and a higher trans‐lamina cribrosa pressure difference when compared to normal subjects. One may, therefore, postulate that a low cerebrospinal fluid pressure may be associated with normal (intraocular) pressure glaucoma. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high trans‐lamina cribrosa pressure difference and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated. This model could explain why patients with normal (intraocular) pressure glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular) pressure glaucoma and eyes with high‐pressure glaucoma, in contrast to eyes with a direct vascular optic neuropathy, show profound similarities in the appearance of the optic nerve head.     

Normotensive glaucoma

Normal tension glaucoma is a form of primary open angle glaucoma where the intraocular pressure remains within the normal range. In this case the main challenge is to establish the correct diagnosis. The clinical evaluation of a patient suspected of a normal tension glaucoma must answer two questions: 1) is the intraocular pressure normal and 2) is it a glaucomatous optic neuropathy or another type of optic neuropathy?     

Development of experimental chronic intraocular hypertension in the rabbit.

There are many unanswered questions about chronic glaucoma which cannot be investigated in the available animal models. The present experiments were designed to develop a rabbit model of chronic intraocular hypertension with characteristics similar to human chronic glaucoma by ligating vortex veins or by making single or multiple intraocular injections of 0.5% or 1% alpha-chymotrypsin, 20% chondroitin sulphate, 2% hydroxypropyl methylcellulose, 2% sodium carboxymethylcellulose or 1% or 2% methylcellulose. Evaluation was based on the clinical findings, intraocular pressure and the retrograde axoplasmic transport function of the optic nerve using a horseradish peroxidase histochemical technique. Most methods either failed to produce moderate chronic intraocular hypertension or were associated with other complications. However, a reliable and relatively long period (eight weeks) of intraocular hypertension was developed by a series of four intra-anterior chamber injections of 1% or 2% methylcellulose. This model has been proved suitable for the study of structural and functional damage to the retina and optic nerve caused by chronic glaucoma.     

Predictive factors for progressive optic nerve damage in various types of chronic open-angle glaucoma

PURPOSE: To evaluate whether various types of chronic open-angle glaucoma differ in predictive factors for progression of glaucomatous optic nerve damage. DESIGN: Observational cohort study. METHODS: SETTING: Prospective observational clinical study. PATIENTS: 517 eyes of 300 Caucasian patients with chronic open-angle glaucoma with elevated intraocular pressure (primary open-angle glaucoma, n = 289; secondary open-angle glaucoma, n = 50) and with normal intraocular pressure (n = 178). OBSERVATION PROCEDURE: During follow-up (median: 49 months, 6 months-130 months), all patients underwent repeated evaluation of color stereo optic disk photographs and white-on-white visual field examination. MAIN OUTCOME MEASURES: Progression of glaucoma was defined as neuroretinal rim loss during the study period. RESULTS: For patients with elevated intraocular pressure, significantly predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim, and larger area of beta zone of parapapillary atrophy. In contrast, in the normal intraocular pressure group, a significant predictive factor was presence of disk hemorrhages at baseline. Within the patients with elevated intraocular pressure, the primary open-angle glaucoma group and the secondary open-angle glaucoma group did not differ in predictive factors for progression of glaucoma. CONCLUSIONS: Open-angle glaucoma patients with normal intraocular pressure and open-angle glaucoma patients with elevated intraocular pressure differ in predictive factors for eventual progression of glaucomatous optic nerve damage. It may have clinical importance and may be helpful in the discussion of the pathogenesis of the glaucomas.     

Differentiating Leber Hereditary Optic Neuropathy from Normal-Tension Glaucoma

Glaucoma is a neurodegenerative disorder characterized by thinning of neuroretinal rim, enlarged cup-to-disc ratio (CDR) and visual field damage. Although raised intraocular pressure is main risk factor for development of glaucoma, it can occur with consistently normal measurements in the intraocular pressure as normal tension glaucoma (NTG). Enlargement of CDR is a classical sign of glaucoma, but it can also result from non-glaucomatous optic neuropathies such as Leber hereditary optic neuropathy (LHON). We describe a case of LHON with increased CDR, discuss its differential diagnosis with NTG and highlight the reasons for misdiagnoses between these two entities.     

Overcoming diagnostic and treatment challenges in uveitic glaucoma

Uveitic glaucoma is a range of disorders that results in optic nerve damage from elevated intraocular pressure secondary to intraocular inflammation. As compared to primary open angle glaucoma, uveitic glaucoma is associated with a more aggressive disease course caused by very high intraocular pressure levels that wax and wane. Diagnosis is often based on clinical presentation, disease course, and associated systemic manifestations. Diagnostic imaging plays an important role in both diagnosis and management. While the mechanisms of uveitic glaucoma vary, treatment requires strict control of the inflammation and may involve additional intraocular pressure lowering techniques. Management often dictates an interdisciplinary approach as systemic association and treatment is common. When topical management does not slow the progression of optic nerve damage and vision loss, surgical intervention is required. A significant portion of patients with uveitic glaucoma will eventually require surgical intervention and the appropriate referrals should be made. By nature, success rates of surgical intervention in uveitic glaucoma patients are lower than non‐inflammatory causes of elevated intraocular pressure and glaucomatous damage. Chronic inflammation, multiple mechanisms, systemic associations, and unpredictable response to treatment make uveitic glaucoma challenging to manage. This review will discuss the pathophysiology, diagnosis, and management of uveitic glaucoma to provide a guide for eye‐care providers.     

Development of experimental chronic intraocular hypertension in the rabbit

There are many unanswered questions about chronic glaucoma which cannot be investigated in the available animal models. The present experiments were designed to develop a rabbit model of chronic intraocular hypertension with characteristics similar to human chronic glaucoma by ligating vortex veins or by making single or multiple intraocular injections of 0.5% or 1%α-chymotrypsin, 20% chondroitin sulphate, 2% hydroxypropyl methylcellulose, 2% sodium carboxymethylcellulose or 1% or 2% methylcellulose. Evaluation was based on the clinical findings, intraocular pressure and the retrograde axoplasmic transport function of the optic nerve using a horseradish peroxidase histochemical technique. Most methods either failed to produce moderate chronic intraocular hypertension or were associated with other complications. However, a reliable and relatively long period (eight weeks) of intraocular hypertension was developed by a series of four intra-anteriar chamber injections of 1% or 2% methylcellulose. This model has been proved suitable for the study of structural and functional damage to the retina and optic nerve caused by chronic glaucoma.     

Fluorescein angiography in chronic simple and low-tension glaucoma.

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.     

准分子激光原位角膜磨镶术眼压的变化和术后青光眼的诊断

准分子激光原位角膜磨镶术（laser in situ keratomileusis,LASIK）是矫正近视最常用的手术方式,术中和术后引起的眼压的变化和术后青光眼的诊断应当引起注意.术中形成的眼压升高,对视盘和视网膜造成潜在的危害.术后中央角膜变薄,导致眼压测量值偏低,易发生青光眼的漏诊.术后长期应用糖皮质激素药物可能引起角膜瓣下层间积液和继发性青光眼.视盘和视网膜神经纤维层检查可能对早期青光眼诊断提供一些参考.     

The optic nerve head in glaucoma: role of astrocytes in tissue remodeling

Primary open angle glaucoma is a common eye disease characterized by loss of the axons of the retinal ganglion cells leading to progressive loss of vision. The site of damage to the axons is at the level of the lamina cribrosa in the optic nerve head. The mechanism of axonal loss is unknown but elevated intraocular pressure and age are the most common factors associated with the disease. Previous studies in human glaucoma and in experimental glaucoma in monkeys have established a relationship between chronic elevation of intraocular pressure and remodeling of the optic nerve head tissues known clinically as cupping of the optic disc. This review focuses on the astrocytes, the major cell type in the optic nerve head. Astrocytes participate actively in the remodeling of neural tissues during development and in disease. In glaucomatous optic neuropathy, astrocytes play a major role in the remodeling of the extracellular matrix of the optic nerve head, synthesize growth factors and other cellular mediators that may affect directly, or indirectly, the axons of the retinal ganglion cells. Due to the architecture of the lamina cribrosa, formed by the cells and the fibroelastic extracellular matrix, astrocytes may respond to changes in intraocular pressure in glaucoma, leading to some of the detrimental events that underlie axonal loss and retinal ganglion cell degeneration.