Tranilast inhibits cell proliferation and collagen synthesis by rabbit corneal and Tenon's capsule fibroblasts

PURPOSE: To determine whether tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, influences cell proliferation and collagen synthesis by rabbit Tenon's capsule fibroblasts (TFs) and corneal stromal fibroblasts (CFs). METHODS: Rabbit TFs and CFs (7000 cells/well) were cultured in F-12 nutrient mixture supplemented with 1% FBS, plus 0, 3, 30, or 300 microM tranilast, and the number of cells was counted 72 hrs later. To determine the effect of tranilast on collagen synthesis, cells at confluence were cultured in a medium containing 0, 3, 30, or 300 microM tranilast and labeled with 3H-proline, and the amount of radioactivity incorporated into collagenase-sensitive proteins was measured. RESULTS: At 300 microM, tranilast decreased the number of TFs by about 27% and the number of CFs by about 45%, but had no effect on cell viability. The same concentration of tranilast reduced TFs collagen synthesis and CFs collagen synthesis. CONCLUSIONS: Tranilast may inhibit scar formation after trabeculectomy for glaucoma and after excimer laser photorefractive keratectomy.     

Anti-allergic drugs inhibit the proliferation of bovine lens epithelial cells in culture

PURPOSE: To examine the inhibitory effects of tranilast, ketotifen fumarate, and disodium cromoglycate which are used clinically as anti-allergic agents, on the growth of bovine lens epithelial cells (LE) in culture. METHODS: LE was grown in Dulbecco's modified Eagle's medium(DMEM) with 10% fetal calf serum and growth was measured with 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide(MTT) and 5-bromo-2'deoxy-uridine(BrdU). Production of collagen, transforming growth factor-beta 1(TGF-beta 1), and basic-fibroblast growth factor(b-FGF) were measured with corresponding enzyme-linked immunosorbent assay(ELISA). Apoptotic cell death was detected by TdT-mediated dUTP-biotin nick end labelling method(TUNEL technique) and the DNA ladder method. RESULTS: Both ketotifen and tranilast inhibited the growth of LE, and half-inhibitory concentrations were 200 microM and 1,000 microM, respectively. Disodium cromoglycate did not inhibit LE proliferation significantly. Ketotifen and tranilast decreased the synthesis of collagen but had no obvious effect on TGF-beta 1 and b-FGF production. Apoptotic cell death was detected in LE treated with ketotifen or tranilast. CONCLUSION: Ketotifen and tranilast may be clinically useful for the prevention of aftercataract. Apoptotic cell death may be involved in the process.     

曲尼司特对青光眼患者体外培养的眼部Tenon囊成纤维细胞增殖和移行的影响

目的 探讨曲尼司特(tranilast)对青光眼患者体外培养的眼部Tenon囊成纤维细胞增殖及移行的影响。方法 取青光眼患者滤过术中剪下的Tenon囊组织,在体外进行成纤维细胞原代及传代培养。分别采用MTT法、细胞计数法、免疫组化加图像分析法及划线法,研究不同浓度的曲尼司特对体外培养的成纤维细胞增殖及移行的影响及其与蛋白激酶C(PKC)表达的关系。结果 当浓度在12．5～100．0mg／L之间变化时,曲尼司特能明显抑制成纤维细胞的增殖,强度呈剂量依赖性;50．0mg／L和100．0mg／L的曲尼司特能明显抑制成纤维细胞的移行,并下调细胞内PKC的表达。结论 曲尼司特能抑制成纤维细胞的增殖及移行,这种作用可能与下调细胞内PKC的表达有关。     

Enhanced short-term plasmid transfection of filtration surgery tissues

PURPOSE: To quantify and localize plasmid transfection of filtration surgery tissues using two delivery techniques. METHODS: Full-thickness filtering procedures were performed on eyes of New Zealand albino rabbits. In 10 eyes, naked plasmid DNA in saline was either injected beneath Tenon's capsule at the filtration site or absorbed into a collagen shield that was then placed external to the sclerostomy and under the Tenon's capsule. Forty-eight hours after surgery, levels of the reporter gene, chloramphenicol acetyltransferase (CAT) were measured in samples of ocular tissues. In two additional eyes, the ss-galactosidase (ss-GAL:) reporter gene expression was localized histologically. RESULTS: Injection of plasmid DNA in saline vehicle into the filtration bleb produced readily detectable CAT activity in bleb tissue (conjunctiva, Tenon's capsule, and sclera) whereas CAT activity was nearly undetectable in samples of the cornea, iris-ciliary body, and tissues located opposite the bleb site. Delivery of the plasmid DNA into the bleb through a collagen shield increased CAT activity 30-fold over injection of plasmid in saline (2711 +/- 567 mU/mg versus 92 +/- 38 mU/mg). ss-Gal activity was imaged only in the region of the bleb, and microscopic examination showed ss-Gal activity localized to Tenon's capsule fibroblasts, with minimal ss-Gal activity observed in inflammatory cells or scleral fibroblasts. CONCLUSIONS: Transfection of filtration tissues is enhanced by absorption of naked DNA into a collagen shield. Furthermore, transfection is localized to the fibroblasts and inflammatory cells of the filtration bleb site. Gene therapy using naked plasmid DNA and a simple collagen shield delivery vehicle may be useful for regulating wound healing after glaucoma surgery.     

Effect of cytokines on regulation of the production of transforming growth factor beta-1 in cultured human Tenon's capsule fibroblasts

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is thought to play a pivotal role in the regulation of the wound healing process after glaucoma filtering surgery. The aim of the present study was to investigate whether platelet-derived growth factor isoforms (PDGF-AA, PDGF-BB), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) modulate the production of latent and/or active TGF-beta1 by cultured human Tenon's capsule fibroblasts (HTF). METHODS: Human Tenon's capsule fibroblasts were seeded at two different densities (30 cells/mm2 and 150 cells/mm2) and stimulated for five days with PDGF-AA, PDGF-BB, bFGF, EGF, IL-1beta and TGF-beta1. Control cells were treated with serum-free medium (WM/F12). The concentrations of latent and active TGF-beta1 in the medium were determined using an immunoassay before and after activation of TGF-beta1 by transient acidification. RESULTS: The concentration of latent TGF-beta1 in conditioned media from HTF seeded at high density (150 cells/mm2) significantly increased after stimulation with 5 ng/ml TGF-beta1 (151.5 +/-41.7 pg/ml) or 10 ng/ml IL-1beta (45.7+/-8.1 pg/ml). The concentration of active TGF-beta1 in conditioned media also significantly increased after stimulation of HTF with 5 ng/ml TGF-beta1 (48.4+/-27.5 pg/ml). CONCLUSIONS: The present results indicate that TGF-beta1 is the most potent inducer of its own synthesis in HTF. Activation of an autocrine TGF-beta1 loop may play a role in the wound healing response after glaucoma filtering surgery.     

Effect of growth factors on the activation of human Tenon's capsule fibroblasts

PURPOSE: To investigate stimulatory effects of PDGF-AA, PDGF-AB, PDGF-BB, bFGF, IL-1beta, TGF-beta1 and TGF-beta2 on the proliferation and myofibroblast transformation of cultured human Tenon's capsule fibroblasts and to characterize expression of PDGF- and TGF-beta-receptors in these cells. METHODS: To determine cell proliferation, cell number of 2nd passage cultured human Tenon's capsule fibroblasts was measured before and after addition of growth factors using a computer-based cell counter system. Immunoblotting was used to detect and quantitate alpha-smooth-muscle actin (alpha-SMA) expression. Expression of PDGF- and TGF-beta-receptor mRNA was detected by RT-PCR, expression of the corresponding protein was demonstrated using Western blot. RESULTS: A significant increase in proliferation (p < or = 0.05) was detected after exogenous stimulation with PDGF-AA (10 ng/ml and 100 ng/ml), PDGF-AB (10 ng/ml and 100 ng/ml), PDGF-BB (10 ng/ml and 100 ng/ml), bFGF (100 ng/ml), IL-1beta (1 ng/ml and 10 ng/ml), TGF-beta1 (0.5 ng/ml) and TGF-beta2 (0.5 ng/ml). Both TGF-beta1 and TGF-beta2 stimulated expression of alpha-SMA in a dose dependent manner with peak activity at a concentration of 50 ng/ml (TGF-beta1) and 500 ng/ml (TGF-beta2). Protein and mRNA of PDGF-receptor type alpha and type beta and TGF-beta-receptors type I, II and III are expressed in cultured human Tenon's capsule fibroblasts. CONCLUSIONS: The present investigation strongly supports the hypothesis that PDGF-isoforms are major stimulators of proliferation of Tenon's capsule fibroblasts after glaucoma filtering surgery while TGF-beta-isoforms are essential for the transformation of Tenon's capsule fibroblasts into myofibroblasts.     

Comparative effects of TGF-beta 1 and TGF-beta 2 on extracellular matrix production, proliferation, migration, and collagen contraction of human Tenon's capsule fibroblasts in pseudoexfoliation and primary open-angle glaucoma

PURPOSE: To comparatively investigate the effects of TGF-beta(1) and TGF-beta(2) on extracellular matrix production, proliferation, migration, and collagen contraction of cultured human Tenon's capsule fibroblasts derived from patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma, primary open-angle glaucoma (POAG), and cataract. METHODS: Tenon's capsule fibroblasts obtained from four groups of patients were cultured and stimulated with different concentrations (0.1-10 ng ml(-1)) of TGF-beta(1) or TGF-beta(2) for up to 14 days. Cell proliferation was determined with the WST-1 colorimetric assay, cell migration by using the Transwell assay system, and collagen contraction by computerised analysis of three-dimensional collagen lattices and immunohistochemistry for alpha-smooth muscle actin expression. Expression and synthesis of extracellular matrix components (fibronectin, collagen types I and III) was assessed by enzyme-linked immunosorbent assays, by real-time RT-PCR, and by transmission electron microscopy. RESULTS: Both TGF-beta(1) and TGF-beta(2) in pathophysiological concentrations of 0.1-5 ng ml(-1) stimulated cell proliferation, migration, collagen contraction, alpha-smooth muscle actin expression as well as mRNA expression and secretion of fibronectin, collagen type I, and collagen type III by Tenon's fibroblasts derived from all groups of patients. TGF-beta stimulation occurred in a concentration-dependent manner with different peak activities associated with different fibroblast functions. There was some variability among the different groups of patients with an increased response of cells derived from PEX and POAG patients as compared to cataract patients. Although no statistically significant differences were found between both TGF-beta isoforms, TGF-beta(1) had a more pronounced stimulatory effect on expression and synthesis of extracellular matrix components including the production of elastic microfibrils, particularly in cells derived from patients with PEX syndrome/glaucoma. CONCLUSIONS: These findings suggest a significant contribution of TGF-beta(1) in addition to TGF-beta(2) to the conjunctival scarring process following glaucoma filtration surgery. Due to its pronounced fibrogenic potential, TGF-beta(1) may become another focus for targeting drug therapy, particularly in patients with PEX glaucoma.     

The development of encapsulated filtering blebs

The development of an encapsulated filtering bleb (Tenon's cyst) complicated 56 of 409 consecutive filtering operations (13.7%) performed during a 40-month period after January 1983. Fifteen eyes (27.8% of encapsulated blebs) required surgical revision. The recognition of bleb encapsulation occurred 20.4 +/- 12.7 days (mean +/- standard deviation) postoperatively. Prolonged duration of beta-adrenergic antagonist therapy was associated with an increased frequency of bleb encapsulation (180.6 +/- 128.5 weeks without encapsulation, 229.0 +/- 129.3 weeks with encapsulation, P less than 0.009). Bleb encapsulation occurred in 42 of 272 eyes with previous argon laser trabeculoplasty, but in only 4 of 85 eyes without any previous anterior segment laser (P less than 0.01). Encapsulated filtering blebs developed in 4 of 12 (33.3%) eyes with congenital glaucoma and 4 of 9 (44.4%) eyes with juvenile glaucoma (P less than 0.0002). The intraocular pressures (IOPs) in the eyes with encapsulated filtering blebs were significantly elevated at 1, 2, and 3 postoperative weeks, and at final follow-up compared with eyes without bleb encapsulation.     

兔眼抗青光眼滤过术中应用C3F8观察滤过道的组织病理学变化

目的:研究小梁切除术中辅助应用C3F8气体后滤过道的病理组织学变化,探讨C3F8改善滤过泡的性状和功能、提高手术成功率的作用机理。方法:将新西兰兔进行小梁切除术随机分为单纯小梁切除术组、小梁切除术组联合C3F8气体组、小梁切除术组联合MMC组;并应用病理组织学和免疫组化技术,对兔眼术后3d,1,2,4wk5个不同时期的滤过泡组织进行病理检查,观察成纤维细胞、新生胶原纤维、新生血管、炎症细胞的改变。结果:C3F8气体组和单纯小梁切除术组术后滤过道新生胶原纤维量、成纤维细胞差异均有统计学意义;MMC组和单纯小梁切除术组术后滤过道新生胶原纤维量、成纤维细胞差异均有统计学意义;C3F8气体和MMC组术后差异无统计学意义。三种不同手术方式术后滤过道的新生血管生长情况和术后5个不同时期的滤过道的炎症细胞进行比较差异都无统计学意义。结论:小梁切除术中应用C3F8气体可在术后早期抑制成纤维细胞增殖和新生胶原纤维的合成,抑制或减轻术后滤过道的疤痕化,提高手术成功率。     

针刺分离结膜下注射干扰素治疗青光眼术后早期包裹囊状泡

目的 观察青光眼滤过手术后早期包裹囊状泡进行针刺分离和泡内注射干扰素α-2b的疗效.方法 对21例(21只眼)早期(术后8～30d)的包裹囊状泡应用干扰素α-2b行滤过泡针刺分离和泡内注射1～5次不等,随访6个月,观察其治疗前、后眼压及滤过泡形态的变化.结果 治疗前眼压平均为(25.82±4.65)mmHg,治疗后为(15.20±5.43)mmHg,治疗前、后眼压差异有统计学意义(t=6.86;P＜0.01).随访1、3、6个月后平均眼压分别为(14.66±4.36)、(13.97±2.69)、(14.98±4.61)mmHg,功能滤过泡形成率80.95%(17/21),条件成功率90.48%(19/21).随访6个月后平均眼压与治疗前的平均眼压之间差异有统计学意义(t=7.59;P＜0.01).结论 应用干扰素a-2b对早期包裹囊状泡行针刺分离和泡内注射治疗可挽救一些频临失败的滤过泡,提高率过性手术的成功率,有较好地疗效,并发症少.     

An Experimental Study on Homoharringtonine Liposome and Glaucoma Filtration Surgery

Purpose: To observe the inhibitory action of homoharringtonine liposome during the healing process of wounds in the filtering sitesMethods: posterior sclerectomies were performed in 14 rabbits. Postoperatively one eye of each rabbit received subconjunctival injections of HH liposome and fellow eye received saline injection in a randomized masked fashion.Results; Fourteen days after operation the IOP of experimental eyes reduced significantly (P < 0.01) as compared with the controlled eyes, and the number of remaining filtering blebs increased noticeably (P< 0.05). Pathohistological examination revealed that the number of fibroblasts per square micron in the filtering sites and the thickness of the scars in the center of the filtering sites of the experimental eyes were less than those of the controlled eyes. No serious ocular toxic and side effects were found.Conclusion : This experiment suggests that homoharringtonine liposome can markedly inhibit the scar formation of filtering sites after glaucoma fi     

晶状体和玻璃体提取物及地塞米松影响Tenon囊成纤维细胞增殖和胶原合成的实验研究

目的　探讨晶状体和玻璃体提取物对猪眼筋膜囊(Tenon囊)成纤维细胞增殖和胶原合成的影响及其在糖皮质激素作用下的变化。方法　体外培养猪眼Tenon囊成纤维细胞,应用噻唑蓝(MTT)比色法和逆转录聚合酶链反应(RT -PCR)法观察在晶状体和玻璃体提取物及地塞米松单独或联合作用下,Tenon囊成纤维细胞增殖和胶原合成的变化。结果　与对照细胞吸光度(A值)(0 .305±0.013)比较, 10mg/L晶状体提取物( 0. 411±0. 000 )和10mg/L玻璃体提取物( 0. 349±0 .027)作用2d即具有促进细胞生长作用,差异有统计学意义(P=0. 00);且随着晶状体提取物、玻璃体提取物浓度的增高,A值相应增加,差异均有统计学意义(P=0. 00)。Ⅰ型胶原的相对含量在晶状体提取物作用细胞内为12 290±231,在玻璃体提取物作用细胞内为10 .853±231,与对照细胞(9389±178)比较,差异均有统计学意义(P<0. 01)。地塞米松对125mg/L晶状体提取物和125mg/L玻璃体提取物作用的Tenon囊成纤维细胞增殖分别具有一定抑制作用,差异有统计学意义(P=0. 00)。地塞米松和提取物联合作用细胞内Ⅰ型胶原的相对含量与提取物单独作用细胞比较,差异均无统计学意义(P>0 .05)。结论　晶状体和玻璃体提取物均可明显刺激Tenon囊成纤维细胞增殖,促进Tenon囊成纤维细胞内胶原合成,     

Effect of tranilast on proliferation,collagen gel contraction,and transforming growth factor beta secretion of retinal pigment epithelial cells and fibroblasts

The efficiency of tranilast for the treatment of proliferative vitreoretinopathy (PVR) was investigated in vitro. A tetrazolium-based colorimetric assay showed that the 300-microM concentration of tranilast inhibited proliferation of bovine retinal pigment epithelial (RPE) cells and rabbit dermal fibroblasts with no toxicity. The contraction of collagen gels embedded with these cells was evaluated in the cultures. Compared with the gel incubated with minimal essential medium and 0.35% bovine serum albumin and/or fetal calf serum, tranilast inhibited gel contraction. Enzyme-linked immunosorbent assay revealed that a 300-microM concentration of tranilast inhibited transforming growth factor-beta(1) (TGF-beta(1)) secretion significantly (p < 0.01). These results suggest that tranilast may inhibit the proliferation of RPE cells and fibroblasts and contraction of intraocular fibrous membranes by suppressing TGF-beta(1) secretion from these cells with a potential to treat PVR.     

Adenoviral-mediated gene transfer to the filtering bleb in rabbits.

PURPOSE: To determine if genes can be transferred to fibroblasts in the filtering bleb using adenoviral vectors. MATERIALS AND METHODS: Twelve New Zealand albino rabbits underwent bilateral full-thickness sclerostomies. On postoperative day 1 an adenoviral vector carrying a reporter gene (lacZ) was injected into the right-eye bleb and saline was injected into the left eye bleb of each rabbit. Three rabbits were euthanized on each of the after days (days 3, 7, 14, and 21). The eyes were enucleated and tissue samples from the filtering bleb were processed for beta-galactosidase activity (a marker for lacZ gene expression) and expression of vimentin (a fibroblast marker). The median number of cells per high-power field with both beta-galactosidase activity and vimentin expression on days 3, 7, 14, and 21 in the right and left eyes were counted to determine adenoviral-mediated gene expression in fibroblasts. RESULTS: In the adenoviral vector-treated eyes, the median number of cells per high-power field with both beta-galactosidase and vimentin expression on days 3, 7, 14, and 21 was 83,100, 1, and 0, respectively. No beta-galactosidase activity was noted in the saline-treated eyes. CONCLUSIONS: Adenoviral vectors can transfer genes to fibroblasts in filtering blebs after glaucoma surgery. The peak efficiency of gene transfer to fibroblasts occurred 7 days after glaucoma surgery. These studies show a potential for genetic manipulation of fibroblast activity in filtering blebs after glaucoma surgery.     

虹膜色素颗粒对兔眼小梁切除术后滤过通道瘢痕化影响的实验研究

目的探讨虹膜色素上皮(iris pigment epithelium,IPE)层色素颗粒对兔眼小梁切除术后滤过通道瘢痕化过程及Tenon囊成纤维细胞增生的影响。设计实验研究。研究对象新西兰大白兔18只。方法单眼做小梁切除手术模型。实验组巩膜瓣下放置0.1 ml(100μg/ml)猪IPE层色素颗粒并保留,阳性对照组和阴性对照组分别放置0.4 mg/ml丝裂霉素C棉片和生理盐水棉片3分钟。术后观察眼压、滤过泡形态30天,并对滤过泡及其周边组织进行组织病理学检查。主要指标眼压、滤过泡形态、手术滤过区瘢痕化程度。结果实验组、阳性对照组、阴性对照组兔眼术前平均眼压分别为(24.78±1.40)、(24.11±1.18)、(24.00±1.53)mmHg(F=0.241,P=0.789)。术后30天平均眼压分别为(20.28±1.87)、(20.39±2.28)、(23.33±1.14)mmHg(F=22.500,P=0.000)。实验组与阳性对照组无显著差异(P=0.86),实验组与阳性对照组均低于阴性对照组(P均=0.000)。滤过泡平均存留时间分别为(28.17±1.72)、(27.00±2.37)、(10.67±1.97)天(F=138.592,P=0.000)。组织病理学检查示实验组和阳性对照组兔眼滤过区结构相似,胶原纤维和瘢痕组织相对较少,而阴性对照组胶原纤维和瘢痕组织明显增生。结论小样本量短期实验研究表明,IPE层色素颗粒可能阻止Tenon囊成纤维细胞增生过程,有助于延缓小梁切除术后滤过通道瘢痕化。     

Inhibitive Effects of Quercetin on Rabbit Tenon Capsule Fibroblasts Proliferation

Purpose:To study the inhibitive effects of quercetin (QU) on the fibroblasts proliferation of rabbit Tenon's capsule and its mechanism. Methods: Cultured fibroblasts were exposed to different concentrations of QU solution and investigated by microculture tetrazolium (MTT) assay. The effect of QU was obser ved on cells cycle using the flow cytometer. Results: QU can suppress the proliferation of rabbit Tenon's capsule fibroblasts in vitro and show a dose-time dependent tendency. Flow cytometer results showed 26.92% cell increase in G1 phase, 23.50% decrease in S phase and 3.42% decrease in G2 phase. Conclusions: QU can suppress the proliferation of rabbit Tenon's capsule fibroblasts in vitro and show a dose-time dependent tendency. QU may effect all phase of cell cycle and inhibit cell proliferation by inhibiting Gl phase transitting to S phase and G2 phase. Eye Science 2005; 21:175-178.     

人工合成白细胞介素-1受体阻断剂CK-17对兔结膜下成纤维细胞的影响

目的研究非甾体类抗炎药物——人工合成白细胞介素-1受体阻断剂CK-17对体外培养的兔Tenon囊成纤维细胞(rabbit Tenon’s capsule fibroblast，RTCF)增生及细胞分泌功能的抑制作用。对CK-17在青光眼滤过术后抗瘢痕增生方面应用的可行性进行探讨。设计体外、对照干预实验研究。研究对象体外培养的兔RTCF。方法用细胞计数的方法检测RTCF增生的情况；用胶原检测试剂盒检测RTCF培养基中分泌的总胶原的含量。主要指标成纤维细胞记数，RTCF培养基中总胶原含量。结果(1)CK-17对RTCF的抑制呈浓度和时间依赖性；(2)CK-17对RTCF胶原分泌的抑制呈浓度和时间依赖性；(3)CK-17在实验浓度下对RTCF无细胞毒性。结论CK-17能够抑制体外培养的兔成纤维细胞增生及细胞总胶原的分泌。     

兔眼滤过术中结膜瓣下辅助应用全氟丙烷后滤过道的组织病理学变化

目的研究小梁切除术中辅助应用全氟丙烷(C3F8)气体后滤过道的组织病理学变化.方法对20只新西兰兔实施小梁切除术.随机分为两组,每组各10只兔(20只眼).第1组随机选择1只眼做单纯小梁切除术,另1只眼做小梁切除术并辅助应用C3F8气体;第2组随机选择1只眼做小梁切除术联合应用丝裂霉素C(MMC),另1只眼做小梁切除术并辅助应用C3F8气体.采用组织病理学和免疫组化技术,对兔眼术后3 d,1、2、3、4周不同时期的滤过泡组织进行病理检查,观察成纤维细胞、新生胶原纤维、新生血管、炎性细胞的改变.结果应用C3F8气体组与单纯小梁切除术组术后滤过道新生胶原纤维量、成纤维细胞量差异均有显著意义(P<0.05);应用MMC组与单纯小梁切除术组术后滤过道新生胶原纤维量、成纤维细胞量差异均有显著意义(P<0.05);应用C3F8气体组与MMC组术后滤过道新生胶原纤维量、成纤维细胞量差异无显著意义(P>0.05).3种不同术式兔眼术后滤过道的新生血管量与术后5个不同时期滤过道的炎性细胞量进行比较,差异均无显著意义(P>0.05).结论小梁切除术中辅助应用C3F8气体可以在术后早期抑制成纤维细胞增殖和新生胶原纤维的合成,抑制或减轻术后滤过道的瘢痕化,从而提高手术的成功率.     

Interferon-gamma inhibits collagen synthesis by human Tenon's capsule fibroblasts in vitro

Collagen deposition is largely responsible for scar information, an undesirable outcome of glaucoma filtering surgery. Because interferon-gamma (IFN-gamma) has been reported to inhibit collagen synthesis in a variety of cells, the authors examined its effect on collagen synthesis by Tenon's capsule fibroblasts cultured from three patients. In addition, the authors studied the effects of IFN-gamma on fibroblast proliferation. IFN-gamma inhibited collagen synthesis at dosages of 1-10,000 U/ml. The average median effective dose (ED50) was 6.60 U/ml. In contrast, IFN-gamma had no significant effect on cell proliferation in dosages of 0.001-10,000 U/ml. These results suggest that IFN-gamma may be a useful agent for modifying the wound healing response, particularly after glaucoma filtering surgery.     

Transconjunctival penetration of mitomycin C

AIMS: The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon's tissue following application over the intact conjunctiva before routine trabeculectomy. SETTINGS AND DESIGN: Institution-based case series. MATERIALS AND METHODS: In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon's capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC). Statistical Analysis Used: Statistical analysis was performed using STATA 8.0 version software (STATA Corporation, Houston, TX, USA). In this study, P -values less than 0.05 were considered as statistically significant. RESULTS: The average weight of the sample of Tenon's tissue excised was 5.51+/-4.42 mg (range: 0.9-17.1) and the average estimated MMC concentration found to be present in Tenon's tissue using HPLC was 18.67+/-32.36 x 10(-6) moles/kg of the tissue (range: 0.38-197.05 x 10(-6)). In 36 of the 41 patients (87.80%), the MMC concentration reached above 2 x 10(-6) moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. CONCLUSIONS: Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs.