MMP-2与近视关系的研究进展

近年来研究表明近视的发生发展与巩膜细胞外基质（ECM）的重塑关系密切,基质金属蛋白酶（MMPs）作为调控巩膜ECM动态平衡最重要的一大酶系,也受到越来越多的重视,其中对于MMP-2的研究最为广泛,作为探讨近视发病机制及治疗的靶因子,不仅有大量研究证明其活性增加与近视发展明显相关,很多通过抑制MMP-2来防治近视的研究也取得了丰硕的成果.现就MMP-2多年来在近视方面的研究进展做一综述.     

MMP-2与近视关系的研究进展

近年来研究表明近视的发生发展与巩膜细胞外基质（ECM）的重塑关系密切,基质金属蛋白酶（MMPs）作为调控巩膜ECM动态平衡最重要的一大酶系,也受到越来越多的重视,其中对于MMP-2的研究最为广泛,作为探讨近视发病机制及治疗的靶因子,不仅有大量研究证明其活性增加与近视发展明显相关,很多通过抑制MMP-2来防治近视的研究也取得了丰硕的成果。现就MMP-2多年来在近视方面的研究进展做一综述。     

环氧化酶-2与脉络膜新生血管

脉络膜新生血管（CNV）是引起视力严重损害的常见原因之一,其发生发展是一个多因子调控、多细胞参与的复杂过程。环氧化酶-2（COX-2）是诱导型环氧化酶,是前列腺素生物合成途径的关键酶。COX-2通过调节血管内皮生长因子（VEGF）的合成及生理功能的发挥、内皮细胞的移行和凋亡,在新生血管的形成过程中起重要作用。近期研究证实,COX-2参与了CNV的形成过程,其抑制剂能够抑制CNV的发生发展,为预防和治疗CNV性疾病提供了新的方向。     

Changes in scleral MMP-2, TIMP-2 and TGFbeta-2 mRNA expression after imposed myopic and hyperopic defocus in chickens

Induction of myopia leads to a decreased glycosaminoglycan synthesis and smaller collagen fibrillar diameters, increased levels of gelatinase-A (MMP-2) and decreased amounts of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the fibrous sclera of both chicks and tree shrews. Another factor found to be involved in altered eye growth is the transforming growth factor beta-2 (TGFbeta-2). The aim of the current study was to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA expression changes separately in the two scleral layers of chicks, following myopic and hyperopic defocus. Chicks were treated unilaterally with positive and negative lenses for different time periods. All contralateral eyes wore plano lenses and additional controls, treated binocularly with plano lenses, were included. Real-time PCR was used to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA levels. Few changes in MMP-2 and TIMP-2 mRNA levels were measured following treatment with plus and minus lenses for up to 3 days. The mRNA levels of MMP-2 and TIMP-2 were either unchanged or co-regulated in both eyes, even though only the eye with the powered lens actually displayed changes in growth. In contrast, TGFbeta-2 mRNA was significantly up-regulated in the cartilaginous layer following treatment with plus lenses after 24 hr, compared to all other groups. These changes were confined to the eyes that also displayed reduced growth, suggesting a role of TGFbeta-2 in the final steps of visual eye growth regulation.     

Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina

PURPOSE: To elucidate the expression pattern of different types of metabotropic P2Y receptors in the adult rat retina. METHODS: Qualitative RT-PCR was used to investigate the expression profile of different P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, and P2Y6), and in situ hybridization studies were performed to show their cellular localization within the retina. Immunohistochemical staining was used to detect the corresponding P2Y proteins (P2Y1, P2Y2, and P2Y4) and their cellular localization. Southern blot analysis and sequencing verified the identity of the P2Y PCR products. RESULTS: RT-PCR revealed the presence of P2Y1, -2, -4, and -6 mRNA in the neural retina and the retinal pigment epithelium (RPE) and choroid. In situ hybridization showed labeling in the retinal ganglion cell layer for all four P2Y receptor subtypes, although the intensity varied. In addition, staining for P2Y1, -4, and -6 mRNA was shown in the inner nuclear layer, but was absent for the P2Y2 receptor subtype. Immunohistochemistry showed intense staining for P2Y1, -2, and -4 in the ganglion cell layer and the outer plexiform layer. There was also a specific subtype staining in the inner plexiform layer (P2Y2, -4), the inner (P2Y1, -4) and outer (P2Y1) nuclear layers and the inner segments of the photoreceptors (P2Y1, -2). discussion. The data suggest that extracellular nucleotides may play complex roles as autocrine-paracrine mediators and may have neuromodulatory effects in the retina through metabotropic P2Y receptors.     

原发性青光眼合并2型糖尿病患者房水及血液中MMP-2及TIMP-2的表达

目的　探讨基质金属蛋白酶２（ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ-２,ＭＭＰ-２）及金属蛋白酶２组织抑制因子（ｔｉｓｓｕｅｉｎｈｉｂｉｔｏｒｏｆｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ-２,ＴＩＭＰ-２）与原发性青光眼合并２型糖尿病的关系。方法　研究对象分Ａ组、Ｂ组、Ｃ组、Ｄ组、Ｅ组、Ｆ组６组,每组３０眼。Ａ组为原发性开角型青光眼（ｐｒｉｍａｒｙｏｐｅｎａｎｇｌｅｇｌａｕｃｏｍａ,ＰＯＡＧ）组,Ｂ组为原发性闭角型青光眼（ｐｒｉｍａｒｙａｎｇｌｅｃｌｏ-ｓｕｒｅｇｌａｕｃｏｍａ,ＰＡＣＧ）组,Ｃ组为ＰＯＡＧ合并２型糖尿病组,Ｄ组为ＰＡＣＧ合并２型糖尿病组,Ｅ组为糖尿病性白内障组,Ｆ组为年龄相关性白内障组。采用酶联免疫吸附试验检测各组房水及血清中ＴＩＭＰ-２及ＭＭＰ-２的含量,并计算ＴＩＭＰ-２／ＭＭＰ-２值。结果　在６组研究对象的房水中,ＭＭＰ-２浓度在Ａ组为（２４．９２±６．６２）μｇ?Ｌ－１、Ｂ组为（３６．８０±１５．０７）μｇ?Ｌ－１、Ｄ组为（２８.４４±５．７８）μｇ?Ｌ－１,均较Ｆ组的（２２．８７±３.５４）μｇ?Ｌ－１显著升高（均为Ｐ＜０．０５）;同时房水中ＴＩＭＰ-２浓度在Ａ组为（４３.９２±１９．５７）μｇ?Ｌ－１、Ｂ组为（７６．１３±２７．６７）μｇ?Ｌ－１、Ｄ组为（６１．９２±６．５１）μｇ?Ｌ－１,也均较Ｆ组的（２２.４８±３．５６）μｇ?Ｌ－１显著升高（均为Ｐ＜０．０５）。Ａ、Ｂ、Ｃ、Ｄ组房水中ＴＩＭＰ-２／ＭＭＰ-２值较Ｅ组和Ｆ组显著提高,约为其２倍,但Ａ组、Ｂ组、Ｃ组、Ｄ组间ＴＩＭＰ-２／ＭＭＰ-２值无显著性差异。在６组研究对象的血清中,Ａ组ＭＭＰ-２和ＴＩＭＰ-２浓度最高,分别为（３９６．７５±４９．３０）μｇ?Ｌ－１和（３３７．６７±６２．７８）μｇ?Ｌ－１,其余各组间ＭＭＰ-２和ＴＩＭＰ-２浓度无显著性差异。６组研究对象血清中ＴＩＭＰ-２／ＭＭＰ-２值无明显差异。结论　原发性青光眼患者中ＴＩＭＰ-２／ＭＭＰ-２值均存在失衡,说明ＭＭＰ-２的活性变化及ＴＩＭＰ-２／ＭＭＰ-２值与ＰＯＡＧ和ＰＡＣＧ的发病密切相关,但２型糖尿病对原发性青光眼的病程进展无明显影响。     

pH and H2O2 concentration of hydrogen peroxide disinfection systems

Hydrogen peroxide disinfection has caused discomfort for some soft contact lens wearers even though the solution was neutralized properly. The discomfort could be due to the endpoint pH of the system used or the residual H2O2 concentration. Using a digital pH meter and H2O2 concentration detection strips, we measured the pH and H2O2 concentration of seven different hydrogen peroxide disinfection systems over their recommended disinfection and neutralization cycles to determine their time courses and endpoint values. The final pH of the seven systems varied from 6.15 to 7.74 pH units. All systems resulted in residual H2O2 concentrations below threshold values. These findings indicated that the final pH may be the cause of patient discomfort after hydrogen peroxide disinfection and neutralization.     

Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma

BACKGROUND/AIM: The authors studied the expression of cancer stem cell surface marker, ABCG2, and neural stem cell marker, MCM2, in retinoblastoma and correlated clinicopathologically. METHODS: Among 39 retinoblastomas, 18 tumours were not subjected to preoperative/postoperative chemotherapy, 15 tumours underwent postoperative chemotherapy, and six tumours had preoperative chemotherapy. There were 20 tumours with no invasion and 19 tumours with invasion of choroid/optic nerve. ABCG2 and MCM2 expression was studied by immunohistochemistry. RESULTS: ABCG2 was positive in six of six and MCM2 was positive in five of six tumours that had recurred in the orbit or metastasised. ABCG2 was positive in 15/19 tumours with invasion. MCM2 was positive in 16/19 tumours with invasion. Invasive tumours showed higher expression of ABCG2 (p < 0.01) and MCM2 (p < 0.01) proteins. There was no correlation with differentiation and laterality of the tumours. Non-neoplastic retina was positive for ABCG2 and MCM2. CONCLUSION: ABCG2 and MCM2 were expressed more in invasive tumours. Further studies are needed to understand the significance of ABCG2 and MCM2 expression in retinoblastoma.     

核因子-E2相关因子2在眼底病中的研究现状与进展

核因子-E2相关因子2（Nrf2）是细胞氧化应激反应中的关键因子,它通过与抗氧化反应元件（A RE）相互作用启动下游抗氧化应激酶和Ⅱ相解毒酶基因表达.Nrf2具有抗炎、免疫抑制、抗凋亡、神经保护等多种作用,与眼底疾病,如年龄相关性黄斑变性、糖尿病视网膜病变、视网膜缺血缺氧性病变密切相关.本文就Nrf2在眼底病中的研究现况与进展进行综述.     

翼状胬肉中MMP-2,TIMP-2和TGF-β1的表达意义

目的:探讨MMP-2及其抑制剂TIMP-2和影响它们作用的TGF-β1在翼状胬肉中的表达及意义。方法:采用Maxvision免疫组化技术检测在20例翼状胬肉和10例正常球结膜中MMP-2、TIMP-2及TGF-β1的表达,并比较两组中表达的差异。结果:MMP-2和TGF-β1在翼状胬肉中的表达的阳性率显著高于正常球结膜中它们的阳性表达率(z=-4.618,-4.376,P<0.01),而TIMP-2在两组中的表达差异无显著性(z=-1.319,P>0.05)。经Spearman等级相关检验分析,在翼状胬肉中,MMP-2和TGF-β1的阳性表达率存在正相关(r=0·686,P<0.01);而MMP-2和TGF-β1与TIMP-2阳性表达率之间无相关(r=-0.410,-0.143,P>0.05)。结论:TGF-β1介导的MMP-2和TIMP-2表达失衡在翼状胬肉的发生、发展及侵犯角膜过程中发挥着重要的作用。     

ACE2 and TMPRSS2 are expressed on the human ocular surface,suggesting susceptibility to SARS-CoV-2 infection

PurposeConjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.MethodsWe analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.ResultsAcross all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.ConclusionsTogether, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.     

单酰甘油酰基转移酶2（MOGAT2）在翼状胬肉组织中的表达及意义

目的　研究单酰甘油酰基转移酶2（monoacylglycerol O-acyltransferase 2,MOGAT2）在翼状胬肉组织中的表达及意义。方法　采用免疫组织化学染色的方法检测54例翼状胬肉组织标本（原发50例,复发4例）和18例正常结膜组织标本中MOGAT2的表达情况,采用半定量积分法分析免疫组织化学表达的强弱,并对结果进行比较及统计学分析,同时分析翼状胬肉组中MOGAT2的表达与年龄、性别等影响因素及临床病理分期之间的关系。结果　免疫组织化学染色结果显示,54例翼状胬肉组织中MOGAT2强阳性表达8例,阳性表达29例,弱阳性表达8例,阴性表达9例;18例正常结膜组织中MOGAT2强阳性表达1例,阳性表达6例,弱阳性表达3例,阴性表达8例。MOGAT2在翼状胬肉组和正常结膜组中的表达差异有统计学意义（Z=-2.403,P=0.016）。在翼状胬肉组中,不同年龄、性别MOGAT2的表达差异均无统计学意义（均为P>0.05）,MOGAT2的表达强度与文化程度、职业、收入、户外工作时是否防护、是否吸烟、饮酒、血糖、血压情况及初、复发均无显著相关性（均为P>0.05）,但与翼状胬肉的临床分期有相关性,进展期翼状胬肉组织中MOGAT2表达显著高于静止期翼状胬肉组织（P<0.05）。结论　MOGAT2在翼状胬肉组织中呈高表达,进展期中的表达强度显著高于静止期,其表达水平的升高可能与翼状胬肉的发生发展有显著相关性。     

EphA2 基因与先天性白内障

先天性白内障多因与晶状体发育相关基因突变造成，其中EphA2基因位于人类染色体1p36，其编码的EphA2酪氨酸激酶受体是一种存在于哺乳动物细胞中的特异性激酶受体，在人类许多组织细胞中都有表达。EphA2酪氨酸激酶受体与晶状体细胞间交流、细胞内蛋白质结构稳定性等多方面相关，其内的SAM结构域可调控晶状体纤维细胞内蛋白募集过程有序。同时，ephrin 配体-EphA2受体复合物正常结合是晶状体纤维细胞纵向排列的先决条件。只有晶状体纤维细胞内蛋白质稳定，相互间规则排列，晶状体才能维持透明性；反之先天性白内障形成。（国际眼科纵览， 2018,  42:   174-178）     

Diabetic papillopathy and type 2 diabetes

CASE REPORT: We report a case of a 62-year-old man with type II diabetes mellitus and mild impairment of visual acuity with bilateral optic disc edema. Visual field examination showed enlargement of right blind spot and an inferior arcuate defect in the left eye. Blood pressure, neuroimaging evaluation and cerebrospinal fluid analysis were normal. Spontaneous resolution was observed six weeks later. DISCUSSION: Although the diabetic papillopathy was initially described in juvenile diabetics, recently an afflicted older subpopulation with type II diabetes has been reported to develop this condition. We discuss the clinical characteristics, pathogenesis and differential diagnosis of this clinical entity.