Upregulation of RAGE and its ligands in proliferative retinal disease

We sought to study the presence of the receptor for advanced glycation endproducts (RAGE) and its ligands, advanced glycation endproducts (AGEs), S100/calgranulins and amphoterin (high mobility group box 1 protein; HMGB1), in the vitreous cavity and epiretinal membranes (ERMs) of eyes of patients with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Undiluted vitreous specimens were collected from 30 eyes of 30 patients undergoing pars plana vitrectomy for repair of retinal detachment (RD) secondary to PDR (n = 15) or PVR (n = 15). The vitreous samples obtained from 10 eyes undergoing macular hole repair were used as controls. Epiretinal membranes were obtained from eight eyes with PDR and from 10 eyes with PVR. The levels of AGEs in the vitreous were measured using ELISA. The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. The vitreous levels of sRAGE were significantly increased in both PDR and PVR (p < or = 0.05) compared to control vitreous. In both PDR and PVR, the vitreous levels of AGEs (p < or = 0.01), S100/calgranulins (p < or = 0.05), and amphoterin (p < or = 0.01) were also elevated compared to control eyes. Expression of RAGE was detected in six of eight ERMs from eyes with PDR and eight of 10 ERMs from eyes with PVR. Many cells expressing RAGE also expressed vimentin, suggesting a glial cell origin. Ligands for RAGE were also detected in ERMs, with AGEs detected in five eyes with PDR and eight eyes with PVR. Similarly, S100 and amphoterin ERM expression was observed in six eyes with PDR; these ligands were also expressed in ERMs from eyes with PVR (8 and 7 cases, respectively). We conclude that RAGE and its ligands are increased in the vitreous cavity of eyes with PDR and PVR and are present in ERMs of eyes with these proliferative retinal disorders. These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases.     

增殖性玻璃体视网膜病变细胞凋亡的信号传导途径研究

目的 :探讨增殖性玻璃体视网膜疾病细胞凋亡的信号传导途径 ,以寻求新的药物治疗途径。方法 :2 3例增殖性玻璃体视网膜病变 (PVR) ,增殖性糖尿病性视网膜病变 (PDR) ,黄斑裂孔 (MH)及黄斑前膜 (MP)的视网膜前膜 (epiretinalmem brane,ERM )由玻璃体切割术中取得。细胞凋亡的情况由terminaldeoxynucleotidyltransfrase dUTP nickendlabeling(TUNEL法 )进行评估。Caspase 3及PARP的表达由特异性抗体抗活性Caspase 3和抗P 85片段的PARP检测。Cytokeratin与抗活性的Caspase 3双染色法进行凋亡细胞类型的鉴别。结果 :大多数发生凋亡的细胞为RPE细胞 ,而凋亡细胞与抗活性Caspase 3和抗P 85片段的PARP表达增加相关。细胞凋亡的数目与发生慢性视网膜脱离 (>2个月 )的病例有关 ,但凋亡系数 (apopto sisindex ,AI)在两组间无显著性差异 (1 4 4 2 9vs 3 2 2 86 ,P =0 1877)。PVR ,PDR ,MP各组的凋亡系数分别为 2 32 5 % ,3 4 2 % ,5 5 % ,P值分别为PPVR&PDR>0 1(0 16 85 ) ,PPDR&MP>0 1(0 5 380 ) ,PPVR&MP>0 1(0 8333)。结论 :此项研究发现细胞凋亡在PVR、PDR、MH及MP发病中的重要调节作用。诱导Caspase 3活性表达可作为一种治疗增殖性视网膜疾病的新的尝试     

Silicone oil in the treatment of complicated retinal detachments

Silicone oil is now used with increasing frequency to treat cases of complicated retinal detachment (RD). The authors report their results using silicone oil in eyes with RD resulting from proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). The retina was completely reattached at last examination in 16 (70%) of 23 eyes with PDR and 20 (67%) of 30 eyes with PVR. Final vision of 5/200 or better was obtained in 5 eyes with PDR (22%) and 16 eyes with PVR (53%) (P = 0.0016). Reproliferation of epiretinal membranes occurred in 26% of diabetics and 23% of eyes with PVR. Silicone oil did not cause regression of iris neovascularization. Complications of silicone oil included corneal decompensation, lens opacification, intraocular pressure elevation, and hypotony.     

Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression

PURPOSE: To assess the incidence of cell proliferation and apoptosis in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and macular pucker (MP) and to further investigate the potential involvement of key executors of apoptosis. METHODS: Epiretinal membranes were obtained from the eyes of 23 patients who underwent vitrectomy surgery for recurrent retinal detachment due to PVR (n = 16), traction retinal detachment due to PDR (n = 5), and macular pucker (n = 2). Cell proliferation was evaluated by Ki-67 and PCNA (proliferation cell nuclear antigen) immunostaining. Apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transfrase-dUTP-nick end labeling). The expression of caspase-3 and PARP (poly-ADP-ribose-polymerase) was detected using antibodies against activated caspase-3 and p85 fragment of PARP. Cytokeratin and activated caspase-3/PARP, GFAP (glial fibrillary acidic protein) and activated caspase-3/PARP double staining were used to identify cell types in the membranes. RESULTS: There was no statistically significant difference in the cell proliferative index between PVR (70.1 +/- 4.2%), PDR (82.1 +/- 7.0%), and macular pucker (72.9 +/- 22.8%) by multivariate analysis (p = 0.39, ANOVA) and univariate analysis. Apoptotic nuclei were seen more frequently in chronic retinal detachments of greater than 2 months duration, but the difference, compared to shorter term retinal detachments was not statistically significant (p = 0.19). The apoptosis indices determined for PVR (2.3 +/- 0.7%), PDR (3.4 +/- 1.5%) and macular pucker (5.5 +/- 3.2%) were not significantly different (ANOVA, p = 0.41). Apoptotic nuclei were correlated, increased with expression of caspase-3 and PARP. Many apoptotic cells appeared to derive from retinal pigment epithelium cells. CONCLUSIONS: Cell proliferation and apoptosis appear to be key mechanisms regulating certain cell populations in epiretinal membranes of PVR, PDR, and macular pucker. Inhibition of proliferative regulators such as PCNA and/or activation of apoptotic executors such as caspase-3 may serve as therapeutic targets to halt progression of proliferative retinal disorders.     

Macrophages in Human Epiretinal and Vitreal Membranes in Patients with Proliferative Intraocular Disorders

Purpose: Macrophages are versatile cells and have been known as a cellular component of epiretinal membranes of proliferative intraocular disorders (PID). However, the origin and functions of these cells in the membranes are not yet clear. In the present study we investigated the characterization of macrophages/monocytes in various types of human epiretinal membranes from patients with proliferative vitreortinopathy (PVR) , proliferative diabetic retinopathy (PDR) and ocular perforating injury by means of immunohistochemical techniques. Methods: A total of 49 epiretinal membranes of PID in which 24 were PDR specimens, 17 were PVR and 8 were proliferations after perforating eye injury were studied. Monoclonal antibodies against human macrophages, monocytes, HLA-DR antigen and interleukin-1 (IL-1) were used. The alkaline phosphatase anti-alkaline phosphatase (APAAP) technique was performed.Results: The results showed that 19 out of 24 PDR specimens (79%), 15 out of 17 PVR specimens (88%) and 7 out of 8 tr     

增殖性糖尿病视网膜病变基质金属蛋白酶的表达

目的:研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)视网膜增殖膜纤维化和新生血管形成与MMP-2和MMP-9异常表达的关系.方法:采用免疫组织化学方法,检测PDR患者20例视网膜前纤维血管膜MMP-2和MMP-9的表达,并与增殖性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)10例非血管性增殖膜进行对比研究.结果:PDR增殖膜MMP-2和MMP-9染色阳性率分别为70%和85%,PVR增殖膜MMP-2和MMP-9染色阳性率分别为80%和60%.在PDR增殖膜上可见血管周围基质MMP-9染色阳性,而且与PVR增殖膜相比,PDR增殖膜MMP-9表达有显著提高.结论:PDR增殖膜MMP-2和MMP-9均有表达,在PDR新生血管形成和纤维化的病理过程中起重要作用.     

三种视网膜病视网膜前膜中基质金属蛋白酶及其天然抑制分子的表达

目的 研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)、增殖性玻璃体视网膜疾病(proliferative vitreoretinopathy,PVR)和急性视网膜坏死(acute retinalnecrosis,ARN)患者视网膜前膜中基质金属蛋白酶(matrixmetalloproteinases:MMPs)及其天然抑制物(tissueinhibitorsofmetalloproteinages,TIMPs)的表达情况.方法 玻璃体手术中剥取PVR、PDR和ARN患者的视网膜前膜,同供体眼视网膜作为正常对照,冰冻切片后进行免疫组织化学染色,包括:MMP-1,MMP-2,MMP-3,MMP-7,MMP-9,TIMP-1和TIMP-2.结果 正常视网膜中能够观察到MMP-1,MMP-3,TIMP-1和TIMP-2的表达,在PVR、PDR和ARN患者标本中各种分子的表达都增强,尤以MMP-2,MMP-3和MMP-7明显.结论 正常视网膜中存在MMPs和TIMPs分子维持着细胞外基质动态的平衡,在PVR,PDR和ARN患者中MMP-2,MMP-3和MMP-7等MMPs分子表达增强,在其病变过程中可能起重要作用.     

Cellular components of proliferative vitreoretinal membranes.

To understand the pathogenesis of proliferative vitreoretinal membrane formation which occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), etc., accurate identification of the cellular components of the membrane is needed. This study was performed to identify cellular components of the membranes by means of immunohistochemical technique. 11 proliferative vitreoretinal membranes which were surgically obtained from 7 eyes with PVR and 4 eyes with PDR were stained with monoclonal antibodies against cytokeratin, glial fibrillary acidic protein (GFAP), or vimentin using immunoperoxidase technique (ABC method). In the PVR membranes, mean cell positivities for cytokeratin, GFAP and vimentin were 48%, 1% and 92%, respectively and in the PDR membranes, 0%, 5% and 93%, respectively. The above results suggest that retinal pigment epithelial cells and fibroblasts are major cellular components of PVR membranes, and that mesenchymal cells are major cellular components and glial cells are minor cellular components of PDR membranes.     

肝细胞生长因子受体在视网膜前膜及培养的人视网膜色素上皮细胞中的表达

目的 观察增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)C、D两级视网膜前膜 (epiretinal membranes, ERM)和培养的人视网膜色素上皮(retinal pigment epithelium, RPE)细胞中肝细胞生长因子受体（hepatocyte growth factor receptor, HGFR）的表达情况。 方法 采用免疫组织化学染色方法对15例复杂孔源性视网膜脱离患者玻璃体切割术中剥离的ERM以及培养的人RPE细胞中HGFR的表达情况进行观察。 结果 在6例PVR C级和9例PVR D级ERM标本中分别有5、7例呈HGFR阳性表达；培养的RPE细胞胞浆中HGFR呈阳性表达。 结论 肝细胞生长因子有可能参与了 PVR的病理过程。 (中华眼底病杂志, 2002, 18: 221-223)     

Basic fibroblast growth factor mRNA, bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders (PVR and PDR)

Basic fibroblast growth factor (bFGF) has been shown to be involved in epiretinal membrane formation in proliferative vitreoretinal disorders. However, up to now, little knowledge exists, as to the actual cellular source of this potent mitogen.We examined 20 epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) (n = 12) and proliferative vitreoretinopathy (PVR) (n = 8) for the presence of bFGF peptide, fibroblast growth factor receptor-1 (FGFR-1) and bFGF messenger ribonucleic acid (mRNA).Using a specific antibody, we detected bFGF peptide in most (8/10) examined PDR membranes and in all (8/8) PVR membranes. Moreover, we found positive staining for the corresponding receptor.Local production of bFGF in epiretinal membranes was confirmed by nonisotopic in situ hybridisation for bFGF mRNA in some (4/7) examined PDR membranes and some (3/4) examined PVR membranes. All membranes which contained bFGF mRNA were also positive for bFGF peptide.In conclusion, bFGF is produced and stored in epiretinal membranes. Together with the corresponding receptor, bFGF may play a role in the auto- and paracrine control of the proliferative processes at the vitroretinal interface.Abbreviations aFGF acidic fibroblast growth factor - bFGF basic fibroblast growth factor - FGFR-1 fibroblast growth factor receptor-1 - mRNA messenger ribonucleic acid     

Proliferative activity in epiretinal membranes. The use of the monoclonal antibody Ki-67 in proliferative vitreoretinal diseases.

Epiretinal membranes occur in a number of pathogenetically different diseases, such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), macular pucker, and ischemic, inflammatory, and degenerative vitreoretinal disorders. The formation of epiretinal membranes is characterized by the proliferation of histogenetically different cell types. Knowledge of the proliferating potential of surgically excised epiretinal membrane tissue might be clinically relevant to determine which patients face a high risk of recurrences. The monoclonal antibody Ki-67 specifically stains a cell-cycle associated nuclear antigen that is only expressed by cells in the G1, S, and G2/M phases of the cell cycle. With this antibody, the actively proliferating growth fraction can be stained in frozen tissue samples of surgically removed epiretinal membranes by the indirect immunoperoxidase method. In this study, the monoclonal antibody Ki-67 was used to screen 37 epiretinal membranes in PVR, PDR, macular pucker, and in recurrences after intraocular silicone oil tamponade for the presence of actively proliferating cells. Additionally, the number of Ki-67 positive cells in a section of the membrane was quantitatively set in relation to the total cell number of this section. Thus a proliferative index (PI) was ascribed to each membrane as a decimal quotient. The proliferative indices can be graded into four subgroups for missing or very low (PI less than 0.1), low (PI 0.1-0.3), moderate (PI 0.3-0.6), and high (PI greater than 0.6) proliferative activities. High proliferative activities were found in 4 of 5 PVR membranes, in 9 of 14 PDR membranes, in 6 of 11 recurrent membranes after intraocular silicone oil tamponade, and in 2 of 6 macular pucker membranes.(ABSTRACT TRUNCATED AT 250 WORDS)     

人玻璃体膜及视网膜前膜免疫组化研究

目的 鉴定人玻璃体膜及视网膜前膜的细胞成分。方法 对增生性玻璃体视网膜病变（ＰＶＲ）１２例和外伤性ＰＶＲ８例患者经玻璃体手术取出的增生膜标本,用鼠抗人角蛋白、波形蛋白、神经胶质纤维酸性蛋白（ＧＦＡＰ）和ＣＤ１４等４种单抗做免疫组织化学ＡＢＳ法染色并观察。结果 １２例ＰＶＲ膜抗角蛋白染色均为阳性,６例抗ＧＦＡＰ阳性,１０例抗ＣＤ１４阳性;８例外伤性ＰＶＲ膜２例抗角蛋白染色阳性,７例抗ＧＦＡＰ阳性,３     

Expression of angiogenic and fibrogenic factors in proliferative vitreoretinal disorders

Purpose To investigate the expression of connective tissue growth factor (CTGF) in the retina of human subjects with diabetes mellitus, and CTGF, CD105, and gelatinase B in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) epiretinal membranes. Methods Twelve donor eyes from six subjects with diabetes mellitus, 10 eyes from five nondiabetic subjects, 14 PDR membranes, and five PVR membranes were studied by immunohistochemical techniques. In situ zymography was used to examine gelatinolytic activity in four PDR membranes. Results In nondiabetic retinas, there was no immunoreactivity for CTGF. Diabetic retinas showed immunoreactivity for CTGF in ganglion cells and microglia. Vascular endothelial cells in PDR membranes expressed CTGF, CD105, and gelatinase B in 10 (71.4%), 11 (78.6%), and 5 (35.7%) membranes, respectively. Myofibroblasts in PDR membranes expressed CTGF, and gelatinase B in 14 (100%), and 6 (42.9%) membranes, respectively. There was a significant correlation between the number of blood vessels expressing the panendothelial marker CD34 and the number of blood vessels expressing CTGF (r = 0.7884; P = 0.0008), and CD105 (r = 0.6901; P = 0.0063), and the number of myofibroblasts expressing CTGF (r = 0.5922; P = 0.0257). There was a significant correlation between the number of myofibroblasts expressing α-smooth muscle actin and the number of myofibroblaasts expressing CTGF (r = 0.8393; P = 0.0002). In situ zymography showed the presence of gelatinolytic activity in vascular endothelial cells in PDR membranes. Myofibroblasts in PVR membranes expressed CTGF, and gelatinase B. Conclusions These results suggest a possible role of CTGF, CD105, and gelatinase B in the pathogenesis of proliferative vitreoretinal disorders.     

Morphological study on the intraocular proliferative membrane of proliferative diabetic retinopathy and proliferative vitreoretinopathy

The membranes from 42 eyes with PDR and 8 eyes with PVR were removed during vitreous surgery. In 12 of those with PDR and 3 of the cases with PVR, the reproliferated membranes formed beneath silicone oil (SO) were removed and were histologically and immunohistochemically examined, using morphometrical quantitative analysis. In each case, area coefficient, fibrous content and the number of new vessels, and thick basement membranes, increased wall cells and multilayer basement membranes of new vessels were studied. In both PDR and PVR, the number of cells per unit area tended to be increased with the period of time after SO was injected, while the percentage of fibrous components did not change. The Percentage of occurrence of each type of new vessels was almost the same in both primary and reproliferative PDR membranes. In the primary proliferative PDR membranes, endothelial cell proliferation was found predominantly, while glial hyperplasia was predominant in the primary proliferated PVR membranes and the reproliferated membranes under SO of PDR and PVR.     

Expression of HLA-DR antigen in epiretinal and vitreous membranes

The pathogenic mechanisms of epiretinal membranes are not clearly understood nowadays in ophthalmology. Trying to elucidate it from another aspect, we examined the presence of HLA-DR antigen in 41 epiretinal membrane specimens from patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) by using immunohistochemical technique (APAAP). The results showed that 82.93% of the membranes (34 out of 41) were HLA-DR antigen positive. HLA-DR antigen was considered to be expressed by macrophages in epiretinal membranes. The findings here reveal that the formation and development of epiretinal membranes are probably correlated with immune responses.     

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.     

糖尿病视网膜前膜中ICAM-1及Mac-1的免疫组织化学研究

目的 观察增生型糖尿病视网膜病变（ＰＤＲ）的纤维增生视网膜前膜（ＥＲＭ）中粘附分子（ＩＣＡＭ－１,Ｍａｃ－１）的表达。方法 用免疫组织化学方法对９例ＰＤＲ患者行玻璃体切割术时剥离的视网膜前膜进行观察。其中糖尿病视网膜病变Ⅳ期４例,Ⅴ期５例。结果 ＩＣＡＭ－１和Ｍａｃ－１在８例视网膜前膜中表达,表达率８９％,ＩＣＡＭ－１和Ｍａｃ－１阳性表达在糖尿病分型及分期中无明显差别。结论 ＩＣＡＭ－１和Ｍａｃ－１在增生型糖尿病视网膜中表达,糖尿病视网膜病变的发病中有粘附分子参与。     

Active scatter factor (HGF/SF) in proliferative vitreoretinal disease

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) possesses mitogenic, motogenic, and morphogenic properties and has recently been implicated in various retinal diseases. The role of HGF/SF in proliferative vitreoretinal disease was investigated. METHODS: Sections of epiretinal membranes were stained immunohistochemically for cytokeratins, to identify HRPE cells, and for HGF/SF receptor (c-Met). Cultured HRPE cells were stained for c-Met and investigated for shape change in response to HGF/SF, by using image analysis. The dose-response relationship for HRPE cells to HGF/SF was investigated by a cell migration assay and the specificity of this response evaluated by a neutralization experiment. Subretinal fluid (SRF) and vitreous from patients with retinal detachment and proliferative vitreoretinopathy (PVR) plus vitreous from eyes obtained after death, eyes with macular hole, and eyes with proliferative diabetic retinopathy (PDR) were investigated for the presence of HGF/SF using an enzyme-linked immunosorbent assay (ELISA). HGF/SF activity was measured using an MDCK cell scatter assay. RESULTS: HRPE cells in epiretinal membranes and in culture expressed c-Met. Cultured HRPE cells responded to HGF/SF by an epithelial-to-mesenchymal shape change and by cell migration, a response that increased with increasing concentrations of HGF/SF. This response was reduced in the presence of neutralizing antibody. There was evidence of HGF/SF in increasing concentrations in more severe PVR and in PDR when measured by ELISA, and, conversely, there was evidence of correspondingly decreasing HGF/SF activity when measured by MDCK cell scatter assay in these diseases. CONCLUSIONS: HGF/SF is present in normal and pathologic vitreous. HRPE cells respond by shape change and cell migration to HGF/SF. Concentrations of HGF/SF increase in proliferative vitreoretinal disease and increase in turn with increased severity of the disease, but HGF/SF bioactivity decreases (consistent with activator depletion). These findings are consistent with the hypothesis that HGF/SF may play a role in the HRPE mesenchymal transformation that typifies PVR.     

人视网膜前膜中粘附分子的免疫组织化学观察

目的 观察增生性玻璃体视网膜病变(Proliferative vitreoreti nopathy，PVR)的视网膜前膜(epiretinal membranes，ERM)中粘附分子(ICAM-1，Mac-1) 的表达。方法用免疫组织化学方法对20例复杂视网膜脱离行玻 璃体切割术时剥离的视网膜前膜进行观察。结果ICAM-1和Mac-1分别在18和15例视网膜前膜中表达，两种粘附分子同在12例视网膜前膜中表达。结论ERM中有ICAM-1和Mac-1的表达，提示粘附分子在PVR的发 生发展中有一定作用。（中华眼底病杂志，2000，16：71-138）     

Detection of eicosanoids in epiretinal membranes of patients suffering from proliferative vitreoretinal diseases

AIM—Arachidonic acid is metabolised via lipoxygenase to 15-HETE (15-hydroxyeicosatetraenoic acid) and 15-HPETE (15-hydroperoxyeicosatetraenoic acid), which are believed to influence proliferation in tissue culture. 15-HETE is the reduction product of 15-HPETE. Cell proliferation is believed to be decreased by 15-HPETE and increased by 15-HETE. The aim of this study was to investigate epiretinal membranes for the presence of these lipoxygenase products and to compare membranes from different disease processes.
METHODS—Epiretinal membranes of 15 patients suffering from proliferative vitreoretinopathy (PVR, n=7) and proliferative diabetic retinopathy (PDR; n=8) were removed during vitrectomy and analysed by means of thin layer chromatography. The plates were evaluated by digital image analysis.
RESULTS—Both 15-HETE and 15-HPETE were identified in membranes from eyes of patients with PVR and PDR with HETE values significantly higher (p<0.05) than HPETE values (HETE/HPETE ratio = 5.2).
CONCLUSION—This study demonstrates that eicosanoids are present in the epiretinal membrane tissue of patients with PVR and PDR. Considering that HETE increases cell proliferation while HPETE inhibits it, it is conceivable that eicosanoids are an additional factor contributing to the regulation of membrane growth in proliferative retinal disorders. Thus, inhibition of lipoxygenase could be a therapeutic approach in these diseases.