角膜内连接结构的研究进展

角膜内连接结构是现今许多角膜研究方面的研究关键,它主要分为细胞细胞连接和细胞基质连接,以细胞细胞连接为主。角膜各层内都存在着细胞细胞连接,各层之间也存在着细胞细胞连接。这些连接在角膜生长发育、稳态保持、损伤修复和角膜疾病中都扮演着重要的角色。我们对角膜内各种连接结构的组成、分布和功能特点,影响因素及临床意义加以综述。     

角膜基质细胞生物学活性与角膜病变

角膜基质细胞是位于角膜基质层中平行排列的胶原纤维板潜在空隙内的扁平细胞。在正常的角膜组织中,角膜基质细胞处于相当稳定的状态。然而,在角膜病变中,角膜基质细胞在发病机制、病理过程及疾病转归中扮演了重要的角色。     

角膜基质透镜在眼科疾病治疗中的应用及展望

随着角膜屈光手术的发展,尤其是飞秒激光的应用,以及临床上角膜供体植片的欠缺,屈光手术中产生的角膜基质透镜逐渐得到眼科医生的关注。新鲜的角膜基质透镜大部分很难立即投入使用,因此对于透镜如何更好的保存与处理是眼科医生需要解决的问题。角膜基质透镜可用于多种眼科疾病的治疗。本文从角膜基质透镜的保存及处理,矫治远视及老视,治疗圆锥角膜、角膜溃疡、角膜营养不良、皮样瘤及复发性翼状胬肉、准分子激光角膜原位磨镶术后所致的角膜变薄,以及覆盖青光眼引流阀防止其暴露等方面就角膜基质透镜在眼科疾病治疗中的应用进行综述,以期为临床深入研究及临床应用提供参考。     

基质金属蛋白酶及其抑制剂与角膜

基质金属蛋白酶（ＭＭＰｓ）是降解细胞外基质成分的主要酶簇，其活性及过度表达与多种角膜疾病有关。本文综述了ＭＭＰｓ的分类、特性、各种角膜疾病中的表达，以及表达与活性调节机制，并总结了各种抑制剂在体内及体外对ＭＭＰｓ的抑制效果。     

SMILE来源的角膜基质透镜研究进展

自飞秒激光小切口角膜基质透镜取出术(small incision lenticule extraction, SMILE)普遍开展以来,术中取出的角膜基质透镜作为副产品已得到广泛的研究和应用,其作为一种良好的生物材料可以在一定程度上弥补角膜材料的匮乏。本文针对SMILE来源的角膜基质透镜的结构特征,各种保存方法如冷冻保存法、无水氯化钙法、甘油保存法等对其厚度、透明度、机械性能等方面的影响,及其在矫正远视和散光,治疗圆锥角膜、角膜穿孔、Mooren溃疡和翼状胬肉共存、角膜皮样瘤、准分子激光角膜原位磨镶术后角膜扩张、青光眼等眼科疾病中的相关应用进行综述,以期为深入研究及临床应用提供参考。     

基质金属蛋白酶与角膜病变

基质金属蛋白酶(MMP)是一族活性依赖金属离子锌并以细胞外基质(ECM)成分为水解底物的复杂蛋白酶家系。在机体的生长发育和许多病理过程,主要与细胞外基质的破坏和重塑有关。许多角膜病变如圆锥角膜、与类风湿病相关的周边溃疡性角膜炎、糖尿病性角膜病变、角膜新生血管、翼状胬肉对角膜组织侵袭等发生发展过程均与基质金属蛋白酶有关,近年来这方面的研究逐渐受到重视,而对基质金属蛋白酶活性表达的干扰更为角膜病变的治疗提供了一个有着广阔前景的途径,现就近年来国外这方面的研究复习如下。     

泪液的临床生物化学

泪膜在眼球表面,对于保护眼球,防止外界影响及维护角膜和结膜的健康起着重要作用。许多疾病可影响泪膜的结构或改变其成分,致影响角膜。以下几种疾病,泪膜异常是其原因或是其结果:干燥性角膜结膜炎(Sj(?)gren综合征)、Riley-Day综合征和自主神经功能失调、先天性无泪、     

角膜基质细胞研究进展

角膜基质细胞,存在于角膜基质层中,在正常情况下,处于静止状态。但当角膜损伤时,不同上皮来源的因子及环境信号,将影响角膜基质细胞的应答反应,决定着角膜能否完全被修复或形成角膜瘢痕。本文就角膜基质细胞的分布、形态、受激后的应答反应情况及与角膜疾病的关系作一综述。     

角膜神经的研究进展

角膜具有丰富的神经末梢,是机体中最敏感的组织之一,对于保持眼表的完整性具有重要作用。业已证实,有许多疾病与角膜神经相关,如角膜炎、干眼征和糖尿病等。本文从角膜神经的起源、研究方法、分布与形态学结构、角膜神经的再生以及相关疾病几个方面对其作一综述。     

角膜新生血管中细胞与分子的研究进展

多种眼部损伤可诱导角膜新生血管形成,促进疾病发展,造成角膜水肿、视力受损,甚至失明,因此抑制角膜新生血管有助于延缓疾病进程并降低角膜损伤,具有十分重要的临床意义。本文将对参与角膜新生血管形成的细胞及分子作最新的系统论述,并分析可能的抑制靶点,以期为科研及临床提供参考。     

基质金属蛋白酶对圆锥角膜的影响

圆锥角膜以进行性角膜前突和变薄,导致不规则散光和视功能损害为特征.大量研究表明,基质金属蛋白酶(matrix metalloproteinases,MMPs)在圆锥角膜基质降解和变薄过程中起关键性作用.紫外光A/核黄素角膜交联术(corneal crosslinking,CXL)是近年来发展起来的唯一能够延缓甚至阻止圆锥角膜病情进展的保守治疗方法.CXL对角膜生物力学和结构的影响研究较多,而对MMPs的影响研究较少.研究表明,CXL后患者泪液中的MMPs出现变化,而对基质中MMPs的影响尚无报道.进一步研究CXL后MMPs的变化有助于理解CXL后圆锥角膜的病理生理进程,以及CXL稳定圆锥角膜病情的作用机制.     

Cellular and molecular events in corneal wound healing: significance of lipid signalling

Alterations in the normal healing process after corneal injury can produce undesirable outcomes that range from corneal haze to ulceration and perforation. Lipids play important roles in the complex inflammatory processes that occur after corneal wounding. While some lipid mediators, such as the lipoxygenase derivatives of arachidonic acid, 12-hydroxyeicosatetraenoic acid (12[S]-HETE and 15[S]-HETE), act as second messengers to promote cell proliferation and are possibly involved in the synthesis of other molecules that suppress inflammation, others, such as platelet-activating factor (PAF), exert their actions through specific receptors, play key roles during sustained corneal inflammation (as might occur with chemical burns), and contribute to tissue destruction and neovascularization. PAF is also a strong inducer of selective metalloproteinases (MMPs) that degrade the extracellular matrix. The use of a new PAF antagonist has shown great promise for the treatment of diffuse lamellar keratitis (DLK) and alkali-burned corneas.     

角膜上皮细胞基底膜的研究进展

角膜上皮细胞基底膜是一层很薄的组织,它的结构与其他部位的基底膜既有相似之处,也有独特的地方,在角膜创伤修复中有着重要的作用.基底膜组织的破坏会导致一系列棘手的角膜病变,而近来对角膜上皮细胞基底膜的研究使我们在这些病变的治疗方面有了新的人手点.就近年来角膜上皮细胞基底膜的研究进展做一综述.     

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

Altered expression of matrix metalloproteinases and their tissue inhibitors as possible contributors to corneal droplet formation in climatic droplet keratopathy

Purpose: Climatic droplet keratopathy (CDK) is an acquired corneal disease characterized by progressive scarring of the cornea. In several corneal diseases, matrix metalloproteinases (MMPs) are upregulated during the degradation of epithelial and stromal tissues. We investigated the levels, degree of activation and molecular forms of MMP‐2, MMP‐9, MMP‐8 and MMP‐13 and their tissue inhibitors TIMP‐1 and TIMP‐2 in tear fluid of patients with CDK. Methods: Seventeen CDK patients and 10 controls living in Argentine Patagonia received a complete eye examination, and MMPs and TIMP‐1/2 were determined by immunofluorometric assay (IFMA), gelatin zymography and quantitative Western immunoblot analysis in tear samples. Results: The MMPs were detected mostly in their latent forms. The levels of MMP‐9 and MMP‐2 were found to be significantly elevated in CDK patients, whereas latent and active MMP‐8 levels were significantly enhanced in controls. There was no significant difference in the level of MMP‐13. TIMPs were found as part of complexes, and the TIMP‐1 levels were significantly lower in patients than controls. Conclusion: Elevated MMP‐2 and MMP‐9 levels have been implicated in the failure of corneal re‐epithelialization, and enhanced MMP‐2 and MMP‐9 levels in CDK patients suggest that these MMPs may play a role in corneal scarring in CDK. Elevated levels of MMP‐8 suggest a defensive role for this MMP in inflammatory reactions associated with recurring corneal traumas. Decreased expression of TIMP‐1 in CDK patients suggest deficient antiproteolytic shield likely to render the corneas of CDK patients vulnerable to enhanced MMPs. Overall, these data suggest a mechanistic link between MMPs and TIMP‐1 level in cornea and tears with corneal scarring in CDK.     

基质金属蛋白酶与眼科疾病的研究进展

基质金属蛋白酶(matrix metalloproteinases,MMPs)属于Zn2+和Ca2+依赖性内肽酶家族,是参与降解细胞外基质(extracellular matrix,ECM)的最重要的蛋白酶。因其参与了多种眼科疾病的病理过程,故对其活化与抑制,以及如何高表达进行研究,可为预防和控制各类眼科疾病的发生发展提供崭新的研究方向,现就其最近的科研进展做一综述。     

Matrix metalloproteinases in disease and repair processes in the anterior segment

The pathogenesis of many anterior segment disorders and ocular complications following surgery are secondary to the wound healing response. The extent of clinical damage observed is closely related to the amount of scarring and tissue contraction. Matrix metalloproteinases (MMPs) are a family of enzymes that play a vital role in all stages of the wound healing process. They degrade all extracellular matrix components and also have the ability to synthesize collagen and extracellular matrix members, and are therefore important in the remodeling of a wound. Overexpression of MMPs results in excessive extracellular matrix degradation, leading to tissue destruction and loss of organ function. In the case of the anterior segment, this may mean the loss of visual function. This review focuses on the role MMPs have in the development of various anterior segment disorders. The importance of MMPs in the wound healing response and its potential modulation to manipulate the scarring response is being recognized, and current developments will be described.     

Role of matrix metalloproteinases in recurrent corneal melting

The aim of this study was to compare the presence and activity of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9 and 13 in human melted and cadaverous corneas. Twelve melted corneal specimens from three patients with rheumatoid arthritis, one patient with ocular cicatricial pemphigoid and one patient with melting attributed to spastic entropion and ten control corneal buttons were used. The presence of MMPs was detected using indirect enzyme immunohistochemistry. The active forms of MMP-2 and -9 and MMP-3 and -7 were examined by gelatin and casein zymography, respectively. The concentrations of active MMP-1 and -3 were measured using activity assays. Increased immunostaining intensity for MMP-1 and -9 was seen in the corneal epithelium and the anterior stroma of all, and for MMP-2, -3, -7 and -8 of almost all, melted corneas compared to the negative or slightly positive staining of the controls. The posterior stroma showed the presence of MMP-1, -2, -3 and -9 in almost all and of MMP-7 and -8 in half of all melted specimens. A markedly higher level of active MMP-2 was detected in six and active MMP-9 in all of eleven pathologic specimens compared to control specimens, using gelatin zymography. The proenzymes of MMP-3 and -7 and the MMP-7 intermediate cleavage product were detected only in melted corneas using casein zymography. Significantly increased MMP-1 and -3 activity was also found in the melted corneas using activity assays. The markedly increased immunostaining for MMP-1, -2, -3, -7, -8 and -9 as well as the elevated levels of the active forms of MMP-1, -2, -3 and -9 in melted corneal specimens from patients with various diagnoses suggest that although different stimuli may trigger the pathways that lead to the destruction of the extracellular matrix, these enzymes could play a subsequent role in this process.     

GM6001对碱烧伤角膜组织中基质金属蛋白酶表达及活性的影响

目的 检测正常和碱烧伤后不同时间角膜组织中明胶酶(MMP-2，MMP-9)和胶原酶(MMP-1)的表达，探讨在角膜融解发生中的作用．方法 兔角膜碱烧伤20眼，分为对照组和GM600l治疗组，于伤后12、24、48、72h，1、2周和1个月取材，酶谱法检测角膜组织中明胶酶MMP-2、MMP-9的表达，Western blot检测胶原酶MMP-1的表达。结果 在正常兔角膜中，仅检测到微弱的明胶酶原MMP-2，碱烧伤后1周后开始明显升高，至烧伤后1个月维持较高水平，并在2周时出现MMP-2活性酶的表达，并持续至烧伤后1个月。明胶酶MMP-9在正常角膜组织中检测不到，但烧伤后24h开始表达，于烧伤后1周达到最高，然后逐渐下降，至伤后1个月已检测不到。胶原酶MMP-1在正常组织中检测为阴性，从伤后24h开始升高，1个月内无下降。GM6001治疗组角膜组织MMP-2、MMP-9及MMP-1的表达均明显低于对照组。结论 基质金属蛋白酶参与碱烧伤角膜组织的融解，GM6001可抑制MMPs的活性，进而抑制角膜融解的发生。