基质金属蛋白酶在视网膜前膜的表达和意义

目的 研究增生性玻璃体视网膜病变（PVR）视网膜前膜中基质金属蛋白酶（MMPs)的表达。探讨MMPs在PVR病理过程中的作用。方法 经扁平部玻璃体切割术（PPV）和膜剥离术取得PVRC3-D3级视网膜前膜21例，免疫组织化学法分析MMP-2和MMP-9在PVR视网膜前膜的表达，同时进行视网膜色素上皮细胞（RPE）和巨噬细胞染色。结果 21例PVR视网膜前膜MMP-2阳性染色15例，MMP-9阳性8例，RPE细胞表达18例，巨噬细胞表达9例。结论 PVR视网膜前膜有MMP-2和MMP-9表达，可能主要由RPE细胞和巨噬细胞分泌，对PVR的发生和发展起重要作用。     

瘦素在增殖性糖尿病性视网膜病变和增殖性玻璃体视网膜病变中的表达

目的 通过检测瘦素在增殖性糖尿病性视网膜病变（proliferative diabetic retinopathy,PDR）和增殖性玻璃体视网膜病变（proliferative vitreous retinopathy,PVR）中的表达,探讨瘦素在PDR、PVR发生、发展过程中可能的调节机制。方法 分别用免疫组织化学染色的方法和酶联免疫吸附实验检测30例PDR患者、20例PVR病变患者眼内视网膜前膜中瘦素的表达,以及患者的血清、眼前房水、玻璃体液中瘦素的浓度。用Chi－Square Tests统计学方法分析和比较PDR、PVR与对照组之间瘦素表达的差异。结果 免疫组织化学染色结果：30例PDR患者中,有18例患者眼内视网膜前膜的瘦素受体呈阳性表达,阳性率为60%,与对照组比较,差异有统计学意义;20例PVR患者中,有3例患者眼内视网膜前膜的瘦素受体呈阳性表达,其中2例为血管纤维性视网膜前膜,1例为细胞纤维性视网膜前膜,阳性率为15%,与对照组比较,差异无统计学意义。ELISA结果：检测30例PDR患者的血清、眼前房水、玻璃体液中瘦素的浓度,与对照组之间差异有统计学意义（P＜0.05）;检测20例PVR患者的血清、眼前房水、玻璃体液中瘦素的浓度,与对照组之间差异无统计学意义（P＞0.05）。结论 瘦素可能主要是通过促进新生血管的生成参与到增殖性糖尿病性视网膜病变的发生、发展中,与增殖性玻璃体视网膜病变的发生、发展无明显相关性。     

增生性玻璃体视网膜病变增生膜中基质金属蛋白酶及其抑制剂的表达

目的研究增生性玻璃体视网膜病变（proliferative vitreoretinopathy，PVR）增生膜中基质金属蛋白酶（matrix metalloproteinases，MMP）及其抑制剂（tissue inhibitors of matrix metalloproteinases，TIMP）的表达。方法采用免疫组织化学技术的SP法，检测PVR增生膜和正常尸眼神经视网膜标本中MMP-2、MMP-9和TIMP-1的表达，光镜观察染色结果。结果41例PVR增生膜标本HE染色切片光镜下可见视网膜色素上皮（retinal pigment epithelial，RPE）细胞、神经胶质细胞、成纤维细胞、巨噬细胞等细胞成分，它们被大量细胞外基质所包绕。视网膜前膜中以RPE细胞为主要增生细胞，视网膜下膜中以神经胶质细胞为主要增生细胞。免疫组织化学染色结果显示：（1）25例PVR增生膜标本表达MMP-2，11例PVR增生膜标本表达MMP-9，14例PVR增生膜标本表达TIMP-1；（2）22例视网膜前膜标本表达MMP-2，3例视网膜下膜标本表达MMP-2，差异有显著性（P〈0．05）；（3）正常尸眼神经视网膜标本中未检测到MMP-2、MMP-9及TIMP-1的表达。结论细胞外基质与PVR增生膜的形成关系密切，MMP-2、MMP-9及TIMP-1在PVR形成过程中发挥重要作用，通过合理地调控MMP和TIMP的平衡，为预防和治疗PVR提供可能性理论依据。     

基质金属蛋白酶与糖尿病视网膜病变新生血管生成

基质金属蛋白酶（MMPS）是新生血管产生的必须条件之一,视网膜新生血管生成是糖尿病视网膜病变增殖期的标志。本文就基质金属蛋白酶的分子生物学特性和其在糖尿病视网膜病变发病过程中的作用作一综述。     

糖尿病及非糖尿病视网膜病变患者玻璃体中 基质金属蛋白酶的表达

目的比较糖尿病视网膜病变(diabetic vitreoretinopathy, DR )及非糖尿病视网膜病变(non-DR)患者玻璃体中基质金属蛋白酶(matrix metalloprote inase, MMP)表达及活性;并探讨MMP表达的相关因素。方法以31例DR、17例non-DR(9例黄斑裂孔,8例视网膜前膜)玻璃体为样本,采用明胶酶谱(Zy mography)技术检测样本中MMP-2、9,并用Western印迹杂交方法证实MMP-2、9表达。结果所有样本中都检测到MMP-2表达,其中DR玻璃体中MMP-2活 性略高于non-DR,但差别无显著性意义。45．2%的DR玻璃体样本中有MMP-9表达,而 non-DR玻璃体样本中无一例有 MMP-9表达。DR玻璃体样本中,部分性玻璃体后脱离(post erior vitreous detachment, PVD)MMP-9表达的阳性率(66．7%)明显高于完全性PVD者( 15．4%)(P<0．01)Western印迹杂交结果进一步证实了MMP-2、9表达。结论DR及non-DR玻璃体样本中MMP-2活性无明显差异;non-DR玻璃体样本中未见MMP-9表达,而DR玻璃体样本中MMP-9表达率与部分性PVD密切相关。MMP-9可能与DR的发生有关。(中华眼底病杂志,2001,17:195-197     

基质金属蛋白酶表达调控与糖尿病视网膜病变的关系

糖尿病视网膜病变(diabetic retinopathy,DR)确切的分子机制尚不清楚,高糖环境可致基质金属蛋白酶(matrix metalloproteinases,MMP)表达增加,MMP是一组锌离子依赖的蛋白水解酶,可以降解几乎所有的细胞外基质成分,在DR中参与了细胞凋亡和新生血管生成过程。在正常生理条件下,MMP活性的调节发生在多水平,包括基因转录调控水平、酶原激活、基质金属蛋白酶组织抑制剂调控水平等。其中基因转录水平的调控是最主要的调控机制。     

基质金属蛋白酶及其组织抑制剂在糖尿病小鼠视网膜组织中的表达

目的:探讨基质金属蛋白酶(MMP-2、MMP-9)及其组织抑制剂(TIMP-2)在糖尿病视网膜病变(DRP)发生发展中的作用及其机制。方法:用免疫组织化学方法和计算机-图像分析技术研究C57BL/KsJdb/db糖尿病小鼠视网膜组织中MMP-2、MMP-9和TIMP-2的表达情况,并观察糖尿病小鼠视网膜毛细血管及其基底膜的超微结构改变,其db/ 型同性同窝瘦型鼠为对照;用SAS软件对实验结果进行统计学处理。结果:随病程进展,糖尿病小鼠视网膜毛细血管基底膜进行性增厚,MMP-2和MMP-9在糖尿病小鼠视网膜组织中的表达显著性降低(P <0.05),而TIMP-2的表达显著性升高(P <0.05),同一病程阶段的MMP-2/TIMP-2的比值显著性降低(P <0.05)。结论:随着病程进展,由于TIMP-2表达的增高,通过与MMP-2以1:1的比例结合成复合物的形式抑制了MMP-2的活性,另外又有MMP-9的表达随病程进展显著下降,这可能是导致DRP早期视网膜毛细血管基底膜进行性增厚的原因。     

玻璃体手术治疗增殖性糖尿病视网膜病变

目的评价玻璃体手术治疗增殖性糖尿病视网膜病变的疗效.方法回顾分析玻璃体手术治疗PDR患者65例80眼的临床资料.随访62眼,随访期3～26个月(平均8.3个月).按Ryan and All标准比较Ⅰ组(玻璃体积血或伴有纤维血管增殖)32眼和Ⅱ组(除玻璃体积血或伴有纤维血管增殖外,合并视网膜脱离)30眼的疗效.结果功能成功工组27眼,Ⅱ组13眼;解剖成功Ⅰ组3眼,Ⅱ组8眼;失败Ⅰ组2眼,Ⅱ组9眼.两组间差异有极显著性(P＜0.001).结论玻璃体手术治疗PDR,仅有玻璃体积血或伴有纤维血管增殖组疗效优于合并有视网膜脱离组,术前光定位不良患眼预后差,手术宜慎重考虑.     

玻璃体手术治疗增殖性糖尿病视网膜病变临床分析

目的 观察手术治疗增殖性糖尿病视网膜病变的治疗效果.方法 对2007～2012年期间在焦作煤业集团中央医院眼科接受玻璃体手术治疗的增殖性糖尿病视网膜病变患者95例(116只眼)进行回顾性分析.入选病例分为3组:第1组为单纯玻璃体积血,第2组为纤维血管性增殖合并局限性视网膜脱离但未累及黄斑组,第3组为视网膜脱离累及黄斑组.对以上3组病例术前术后最佳矫正视力进行统计学分析.结果 第1组术后最佳矫正视力改善率为78.9％;第2组术后最佳矫正视力改善率为80.0％;第3组手术后最佳矫正视力改善率为53.5％.第1组与第2组的视力改善情况经x2检验,差异无统计学意义(P=0.911);第3组视力改善情况与第1组、第2组比,差异有统计学意义(P值分别为0.016、0.014).结论 在黄斑未明显受累时,玻璃体手术治疗增殖性糖尿病视网膜病变可获得较为理想的视力预后.     

糖尿病玻璃体性状特点及其与增殖性糖尿病视网膜病变的关系

糖尿病患者体内持续的高血糖及相应的病理状态不仅会导致糖尿病视网膜病变(DR),也会影响玻璃体代谢,导致糖尿病玻璃体病变。由于玻璃体与视网膜在解剖位置上毗邻,因此糖尿病玻璃体病变与DR在发生发展方面相互促进,特别是玻璃体后脱离(PVD)和玻璃体劈裂等玻璃体视网膜界面的改变,为纤维血管增殖膜的生长提供了支架,并与玻璃体切割术(PPV)术中操作密切相关。本文整理了糖尿病患者玻璃体结构及胶原交联产物改变、玻璃体视网膜界面改变及其与增殖性糖尿病视网膜病变(PDR)关系的相关研究,旨在深入了解糖尿病玻璃体病变,为DR的研究和治疗、PPV手术方案的制定等提供参考。     

糖尿病视网膜病变发病机制的研究进展

糖尿病视网膜病变是糖尿病的重要并发症之一,它与高血糖、多元醇代谢异常、蛋白质非酶糖化、细胞凋亡、DG2PKC系统的激活、细胞因子及自由基作用等多种因素有关。本研究就其病理、发病机制作一综述。     

增殖性糖尿病视网膜病变玻璃体手术并发症分析

目的:探讨糖尿病视网膜病变玻璃体手术并发症及防治。方法:82眼增殖性糖尿病视网膜病变行玻璃体手术治疗,并随访3~24mo,对其术中和术后并发症进行回顾性分析。结果:术后视力较术前不同程度的提高者62眼(72%),但部分患眼出现不同情况的并发症,包括高眼压、玻璃体出血、并发性白内障、医源性视网膜损伤等。结论:糖尿病视网膜病变进行玻璃体手术能挽救大多数眼球并恢复一定的有用视力,但对手术并发症应重视并积极预防治疗,以提高玻璃体手术的效果。     

Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy

AIM: To examine epiretinal membranes of proliferative diabetic retinopathy (PDR) for the presence of selective matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), in order to determine whether neovascularisation and fibrosis, characteristic of this complication of diabetes mellitus, are associated with specific anomalies of MMP or TIMP expression. METHODS: The presence of selected MMPs and TIMPs was investigated in 24 fibrovascular epiretinal membranes of PDR, and the findings compared with that observed in 21 avascular epiretinal membranes of proliferative vitreoretinopathy (PVR) and five normal retinas. Specimens were examined for deposition of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and TIMP-3). RESULTS: The results showed that unlike normal retina, which constitutively expresses MMP-1 and TIMP-2, a large proportion of PDR membranes (> 62%) stained for MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-3. There were no differences in the expression of these molecules when compared with PVR membranes. A characteristic staining for MMP-9 was observed within the perivascular matrix of PDR membranes, and there was a significant increase in TIMP-2 expression by PDR membranes (p= 0.036) when compared with PVR membranes. CONCLUSIONS: The findings that MMPs involved in degradation of fibrovascular tissue matrix, as well as TIMP-1 and TIMP-2, are found in a large proportion of PDR membranes, and that their expression does not differ from that of PVR membranes, suggest the existence of common pathways of extracellular matrix degradation in pathological processes leading to retinal neovascularisation and fibrosis.     

Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

AIM: To assess the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR).METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group (n=16) did not receive IVR, while IVR group (n=26) underwent IVR 5d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin (H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density (MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein (GFAP) and α-smooth muscle actin (α-SMA) as markers of glial-mesenchymal transition (GMT). The GMT index (GI; ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs.RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups (P>0.05). The MVD of the IVR group (130.62±15.46/mm2) was significantly lower than that of the controls (142.25±19.16/mm2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson’s correlation coefficients (PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls (P<0.05). GI in the IVR group (1.10±0.10) was significantly lower than in the controls (1.21±0.12, P<0.05).CONCLUSION: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR.     

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. CONCLUSION: FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.     

增生型糖尿病视网膜病变纤维化相关因子的研究进展

增生型糖尿病视网膜病变（PDR）纤维血管膜的形成严重损害患者的视力,其发生、发展与许多细胞因子的相互作用有关,如转化生长因子（TGF）、结缔组织生长因子（CTGF）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、血小板源性生长因子（PDGF）、肿瘤坏死因子（TNF）、细胞外基质（ECM）、基质金属蛋白酶（MMPs）和其他如内皮素、趋化因子等。因此,PDR纤维血管膜的形成机制非常复杂。就PDR纤维化的发生与细胞因子、ECM、MMPs及其他因素关系的研究进展进行总结。     

Development of macular holes in diabetic retinopathy with fibrovascular proliferation: Report of four cases

There are yet no reports in the literature describing the mechanism of macular hole (MH) formation associated with fibrovascular proliferation in proliferative diabetic retinopathy. We report four cases of MHs in diabetic retinopathy with fibrovascular proliferation; formation of MHs were studied using sequential pre-MH optical coherence tomography (OCT). In Case 1, initial OCT revealed tractional schisis and cysts with fovea detachment. An MH with bowl-shaped detachment was noted within 6 weeks. In Case 2, initial OCT revealed thickened posterior hyaloid membrane with vitreomacular traction. Five and a half years later, OCT showed MH formation with possible vitreomacular separation. Some epiretinal membrane was also noted in the macula area. In Case 3, initial OCT revealed tractional retinal elevation from the superonasal area to the fovea with macular thinning. An MH with detachment developed 7 weeks later. In Case 4, initial OCT revealed macula-involved retinal detachment with traction. An MH was noted 4 weeks later. The analysis of sequential OCT findings in these four cases suggests that strong vitreoretinal adhesion and traction of fibrovascular proliferation may induce an MH without going through the same evolutionary phases as those characteristic of idiopathic MHs.     

结缔组织生长因子mRNA在增生性糖尿病视网膜病变视网膜前纤维血管膜中的表达

目的：观察结缔组织生长因子（connective tissue growth factor ,CTGF)mRNA在增生性糖尿病视网膜病变（proliferative diabetic retinopathy,PDR)纤维血管性视网膜前膜中的表达。方法：采用原位杂交方法，对玻璃体切割术获得的6例PDR的纤维血管性膜进行CTGF mRNA的检测。结果：2例纤维血管性膜标记为阳性染色（＋＋），4例为强阳性染色（＋＋＋），每例标本随机计数100个细胞中的阳性细胞数，取6例标本的平均值，计算平均阳性率为77％，阳性细胞多见于成纤维细胞样细胞和新生血管的血管内皮细胞。结论：PDR纤维血管性膜形成过程中成纤维样细胞及血管内皮细胞在TGF－β等生长因子的刺激下，CTGF mRNA显著上调，CTGF参与了PDR纤维血管性膜的形成和发展。