Expression of bone morphogenetic proteins (BMPs), their receptors, and activins in normal and scarred conjunctiva: role of BMP-6 and activin-A in conjunctival scarring?

Bone morphogenetic proteins (BMPs) and activins are multifunctional growth factors, which also affect wound healing and tissue fibrosis. To determine their putative role in conjunctival wound healing and scarring, we investigated the expression of various BMPs, BMP receptors, and activins in normal and scarred human conjunctival tissue and in cultured human Tenon's capsule fibroblasts on the mRNA and protein level. Messenger RNA expression of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, the BMP receptors type I (BMPR-IA, BMPR-IB) and II (BMPR-II), and of activin A and B was investigated by semi-quantitative RT-PCR in normal conjunctival specimens and in scarred filtering blebs as well as in cultured Tenon's capsule fibroblasts obtained from patients with primary open-angle glaucoma (POAG), pseudoexfoliation (PEX) glaucoma and cataract. Immunohistochemistry was used to study the protein expression of BMP-2, BMP-4, BMP-6, BMP-7, and activin A in normal and scarred conjunctival tissue as well as in cultured Tenon's capsule fibroblasts. BMP-2, BMP-3, BMP-4, BMP-6, BMP-7, all BMP receptors, and activin A were expressed on the mRNA and protein level in conjunctival biopsies without showing any differences between groups of patients. The mRNA and protein expression of both BMP-6 and activin A was found to be significantly increased in scar tissue compared with normal conjunctiva and could be immunolocalized to epithelial cells, vascular endothelia, stromal fibroblasts, and macrophage-like cells. However, no significant increase in receptor gene expression was observed in scar tissue. With the exception of BMP-7, all growth factors and receptors were also expressed in cultured Tenon's fibroblasts without showing any differences between cultures derived from normal and scarred conjunctival specimens. These findings suggest various BMPs and activin A as components of the conjunctival cytokine meshwork regulating tissue homeostasis and wound healing and provide evidence that alterations in the expression of BMP-6 and activin A, in particular, are associated with conjunctival scarring. Modulation of BMP/activin activities may, therefore, be explored as new approaches for managing postoperative conjunctival scarring responses in glaucoma patients.     

不同术式治疗翼状胬肉的疗效分析

目的:比较巩膜暴露法、带球结膜瓣的角膜缘干细胞移植术、带球结膜瓣的角膜缘干细胞移植术联合术中封闭球结膜与Tenon囊之间间隙的手术方式治疗翼状胬肉的临床疗效。方法:翼状胬肉患者130例138眼,分为三组:A组(45例,48眼):采用巩膜暴露法行翼状胬肉切除术;B组(42例,45眼):带球结膜瓣的角膜缘干细胞移植术;C组(43例,45眼):翼状胬肉切除联合带球结膜瓣的角膜缘干细胞移植术及封闭球结膜与Tenon囊之间间隙。术后随访12mo。结果:三组复发率分别为27.1%,8.9%,4.4%。A组与其余两组比较存在显著差异(P<0.05),B组与C组存在差异,但无统计学意义。肉芽肿形成:A组3眼,B组2眼,C组未见。C组泪阜的形态及位置明显优于A组及B组。结论:带球结膜瓣的角膜缘干细胞移植术联合术中封闭球结膜与Tenon囊之间间隙能显著降低翼状胬肉术后复发率,减轻炎症反应,预防肉芽肿的形成,有助于恢复泪阜的正常形态及位置,是目前治疗翼状胬肉的较理想手术方式。     

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.     

Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon's capsule in glaucomatous patients

Conjunctival and Tenon's capsule biopsies from two patient groups were quantitatively analyzed by light microscopy. Group A consisted of 20 patients with a primary glaucoma for whom surgery was a planned primary treatment modality. Group B was comprised of 20 patients with a primary glaucoma who had received at least two types of antiglaucoma topical medication, for a minimum of 1 year (mean, 7.7 years) before surgery. All slides were examined by two masked observers. A significant increase in the number of macrophages, lymphocytes, mast cells, and fibroblasts in the conjunctiva and Tenon's capsule and a significant decrease in the number of epithelial goblet cells were seen in the group that received long-term drop therapy. These results suggest that exhaustive medical therapy, before surgery is offered, increases the number of tissue inflammatory cells. It is possible this may enhance the risk of external bleb scarring and filtration surgery failure.     

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,     

羟基磷灰石义眼台植入术临床应用

目的探讨眼球摘除或眼内容剜除羟基磷灰石义眼台植入术临床应用。方法眼内容剜除,后巩膜开窗,羟基磷灰石义眼台植入巩膜腔或肌锥内,分层紧密缝合巩膜、筋膜及结膜。结果2例2眼义眼台轻度外露,观察随访半年无发展,后行羊膜移植后愈合,其余21例21眼均无结膜裂开及义眼台外露,取得了满意的效果。结论眼内容剜除后一期植入义眼台于巩膜腔或肌锥内,术中充分降低巩膜、筋膜及结膜的张力,并紧密分层缝合是降低和预防结膜裂开,义眼台外露、脱出的关键。     

汉防己甲素诱导人眼Tenon囊成纤维细胞的凋亡效应

目的 研究汉防己甲素(Tet)抑制人眼Tenon囊成纤维细胞(TCFs)的凋亡效应.方法 用组织块混合消化液培养法体外培养人眼TCFs,并对培养的传代细胞进行形态学鉴定.通过透射电镜、TUNEL法和流式细胞仪观察Tet抑制人眼TCFs的凋亡作用.结果 人眼TCFs体外生长良好.透射电镜下见Tet处理后的人眼TCFs细胞质固缩,呈现凋亡表现;TUNEL法可见Tet组出现大量的阳性凋亡细胞;流式细胞仪检测TCFs经Tet作用后G_0/G_1期细胞减少22.2%,S期细胞增加20.53%,G_2/M期细胞增加1.6%,Tet抑制TCFs细胞周期于G1期,Tet组凋亡率明显高于对照组(P=0.000).结论 Tet可以诱导人眼TCFs发生凋亡,进而发挥其抑制增生的作用.     

角膜缘小切口小梁切除术的设计及临床观察

目的　探讨角膜缘小切口小梁切除术的方法并观察其治疗各型原发性青光眼的效果。方法　结膜止点切开 ,切口长 4.0mm ;角膜缘前界板层切开 ,切口长 3 .5mm ;角巩膜瓣下阶梯状小梁切除联合浅层巩膜切开及深层巩膜表面中部纵向电凝。对术后视力、眼压、滤过泡及手术并发症进行总结。结果　术后随访 6～ 42月 ,所有病例角膜上皮无损伤 ,角膜缘切口无渗漏 ,3 4例 ( 46眼 )中 43眼滤过泡扁平弥散 ,3眼滤过泡不明显 ,眼压平均为 ( 16.78± 4.3 8)mmHg( 1mmHg =0 13 3kPa)。结论　该手术方法操作简便、组织损伤小 ,降低了滤过道瘢痕形成的发生率     

Inhibition of conjunctival scarring and contraction by a porous collagen-glycosaminoglycan implant

PURPOSE: To study the healing processes of full-thickness wounds in the adult rabbit conjunctiva after grafting with a porous collagen-glycosaminoglycan (CG) copolymer matrix. METHODS: A 7-mm trephine was used to produce lesions of the bulbar conjunctiva down to the level of the bare sclera. Full-thickness removal of the conjunctiva and Tenon's capsule created a reproducible wound bed. Wounds either remained ungrafted (control) or were grafted with CG matrix. In previous studies, this CG matrix has induced partial regeneration of the dermis in the human, the swine, and the guinea pig. Healing of the conjunctival epithelium and underlying stroma was evaluated by histology, immunohistochemistry, and measurement of wound contraction kinetics. RESULTS: By 28 days, ungrafted wounds had closed by contraction (26.4% +/- 5.0% fornix shortening) and the formation of scarlike tissue comprising an aligned array of dense collagen populated with occasional fibroblasts. Grafting of identical defects with CG copolymer matrix resulted in inhibition of wound contraction (6.8% +/- 3.2% fornix shortening) and the formation of a tissue that resembled normal conjunctival stroma, being composed of a loose network of collagen fibers and fibroblasts. Contractile fibroblasts (myofibroblasts) were identified at the edge of both ungrafted and grafted wounds during the period of active contraction. Both ungrafted and grafted wounds were completely re-epithelialized by 28 days. CONCLUSIONS: Implantation of CG copolymer matrix drastically reduced contraction and promoted the formation of a nearly normal subconjunctival stroma.     

Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits

PURPOSE: To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. METHODS: Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (io animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. RESULTS: MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. CONCLUSIONS: MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.     

20-gauge transconjunctival pars plana vitrectomy.

This article describes a transconjunctival technique for pars plana vitrectomy using 20-gauge instruments. Sclerotomies are performed directly through the conjunctiva, Tenon's capsule, and sclera with a 19-gauge microvitreoretinal blade. A sutureless 20-gauge infusion cannula is then inserted and pars plana vitrectomy is performed in a standardized fashion using 20-gauge instruments. Each sclerotomy and its corresponding conjunctival incision is closed with a single stitch using a 7-0 polyglactin suture. This transconjunctival technique is a reasonable alternative surgical approach to minimize surgical trauma of tissues (eg, conjunctiva) and hasten postoperative recovery without the additional risks and costs associated with 25-gauge pars plana vitrectomy.     

A comparison of glaucoma drainage implant tube coverage

PURPOSE: Surgeons may use various materials, including donor sclera, dura, or pericardium grafts to cover glaucoma drainage implant tubes, prior to repositioning conjunctiva. We reviewed our experience with these materials. PATIENTS AND METHODS: Sixty-four eyes with at least 24 months follow-up status post glaucoma drainage implant surgery were evaluated for signs of tube erosion, as well as patch graft thinning, after initial placement of donor sclera (23), dura (18), or pericardium (23) patch grafts. RESULTS: Sixty-two eyes required no intervention for conjunctival and patch graft melting with subsequent tube erosion. Three cases (two eyes) of erosion requiring reoperation (1-dura at 6 months, 1-sclera at 15 months, and in the same eye 21 months later, 1-pericardium) were noted. Significant thinning of the donor patch graft such that the tube was visible beneath intact conjunctiva ocurred in 6 out of 23 donor sclera eyes, 4 out of 18 donor dura eyes, and 6 out of 23 donor pericardium eyes. CONCLUSION: No material was more prone to melting than another. Donor sclera may be slightly more cost-efficient, but gamma-irradiated pericardium has sterility advantages.     

Surgery of Tenon's capsule in squint operations]

There is a good chance to reduce the scaring between conjunctiva, Tenon's capsule, muscle and sclera after surgical treatment of rectus and oblique muscles if a careful reconstruction of Tenon's capsule is made. In the rare cases that you have to reoperate, you will experience the benefit of these additional stitches (7-0 vicryl) that restore the integrity of Tenon.     

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.     

New surgical approach for superior conjunctivochalasis

PURPOSE: To show poor adhesion between the conjunctiva and the sclera in eyes with superior conjunctivochalasis (CCh) and to introduce a new surgical approach by reinforcing adhesion between the conjunctiva and the sclera for correcting this deficiency. METHODS: After conjunctival peritomy and removal of the loose Tenon remnants, "Tenon reinforcement" for conjunctival adhesion to the underlying sclera was achieved by transplantation of cryopreserved amniotic membrane with fibrin glue (group A, 9 eyes of 6 patients) or 10-0 nylon sutures (group B, 8 eyes of 6 patients) in 17 eyes of 12 patients with refractory superior CCh. RESULTS: The mean age of patients was 68.2 +/- 9.8 years (range, 54-80 years). Superior CCh was associated with a superior limbic keratoconjunctivitis (SLK)-like clinical feature before surgery and found to exhibit dissolved Tenon capsule during surgery in all patients. During a mean follow-up of 3.7 +/- 1.9 months after surgery, all eyes achieved smooth conjunctival surface without any sign of CCh. Complete resolution of symptoms was seen in 9 eyes (52.9%) and significant resolution in 8 eyes (47.1%). There was no significant difference between groups A and B in improvement of symptoms and signs. No complications related to surgery were noted during follow-up. CONCLUSIONS: We propose that loose and dissolved Tenon tissue is correlated with the development of superior CCh, which may result in an SLK-like appearance by blink-related microtrauma. Reinforcement of conjunctival adhesion onto the sclera by amniotic membrane with either fibrin glue or sutures is effective in alleviating symptoms and signs in eyes with superior CCh.     

RNA干扰技术抑制体外培养的人眼球筋膜囊成纤维细胞增殖的初步研究

目的 探讨RNA干扰技术对体外培养的人眼球筋膜囊成纤维细胞增殖的抑制作用。方法 采用化学合成的靶向IKK-β的siRNA,转染体外培养的人眼球筋膜囊成纤维细胞,同时以对任何基因均无作用的siRNA作为阴性对照。以逆转录聚合酶链反应（RT—PCR）技术检测IKK-βmRNA表达水平,免疫印迹法检测IKK-β蛋白表达水平。将siRNA的转染浓度分别设为5、10、25、50、100、200nmol／L,进行转染,于转染后48h采用四甲基偶氮唑盐法检测其转染后对成纤维细胞的抑制作用。结果 经转染了靶向IKK-β的siRNA,其成纤维细胞IKK-β的mRNA和蛋白表达水平均受到抑制。各个转染浓度（5、10、25、50、100、200nmol／L）均可抑制成纤维细胞的增殖（P〈0．05）,抑制率分别为10．72％、23．35％、30．84％、51．25％、50．06％、49．63％,50nmol／L时已达最大抑制率。结论 靶向IKK-β的siRNA转染可以降低IKK-β的表达水平,同时对体外培养的人眼球筋膜囊成纤维细胞的增殖具有抑制作用。抗IKK-β的RNA干扰技术可能是抑制抗青光眼术后滤过道瘢痕化的新手段。     

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.     

体外转染γ-干扰素基因抑制人眼球筋膜囊成纤维细胞的研究

目的探讨阳离子脂质体介导的γ-干扰素(IFN-γ)基因对体外培养的人眼球筋膜囊成纤维细胞增殖的抑制作用。方法采用脂质体介导的方法,以质粒pcDNA3 IFN-γ基因转染体外培养的人眼球筋膜囊成纤维细胞,同时以空载体重组质粒pcDNA3作为对照,G418筛选抗性克隆并扩增。以RT-PCR、免疫组化及流式细胞仪间接免疫荧光法检测IFN-γ基因的表达,应用流式细胞仪进行细胞周期分析,采用四甲基偶氮唑盐法检测IFN-γ基因对成纤维细胞的作用。结果转染pcDNA3 IFN-γ基因的成纤维细胞在转录水平和蛋白水平表达IFN-γ基因,转染的IFN-γ基因可明显抑制成纤维细胞的增殖。结论转染的IFN-γ基因对体外培养的人眼球筋膜囊成纤维细胞的增殖具有抑制作用。     

Inhibition of Tenon's fibroblast proliferation and enhancement of filtration surgery in rabbits with cytosine arabinoside.

Our purpose was to study the antiproliferative effect of cytosine arabinoside (Ara-C) on rabbit Tenon's fibroblasts and the efficacy of Ara-C as an adjunctive antifibrosis treatment for glaucoma filtration surgery in the rabbit eye. Rabbit Tenon's fibroblasts were exposed to 1 microg/ml of Ara-C for various time intervals, then cell number and viability was assessed at different time points. Following posterior lip sclerectomy, rabbit eyes were treated with 10 mg subconjunctival Ara-C daily for 7 days, then every other day for 7 days. Rabbit fibroblasts exposed to 1 microg/ml Ara-C for 1 hour showed no significant decrease in cell number compared with control. Continuous or 24-hour incubation of fibroblasts with Ara-C was lethal to the cells. Exposure of cells to Ara-C for 3-, 6-, and 9-hour intervals caused significant reduction of cell proliferation. Pulsed treatment of cells with 6 hour exposure to 1 microg/ml Ara-C every 3 days caused prolonged suppression of cell proliferation. Following posterior lip sclerectomy in rabbits, topical instillation of Ara-C drops at varying concentrations and dosing intervals did not cause any significant lowering of intraocular pressure compared with control eyes, although bleb survival was prolonged in eyes treated with Ara-C (P < 0.01). In rabbit eyes treated postoperatively with subconjunctival injections of 10 mg Ara-C every other day for two weeks, the mean intraocular pressure was significantly decreased and the bleb survival time was significantly prolonged (P < 0.0067) compared with control eyes. In conclusion, Ara-C inhibits rabbit Tenon's fibroblast proliferation in vitro. Postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit.     

Anti-allergic drugs inhibit the proliferation of human Tenon's capsule fibroblast and maintain the experimental filtering blebs on rabbit eyes

PURPOSE: To examine whether tranilast and ketotifen fumarate inhibit the growth of human Tenon's capsule fibroblasts and maintain experimental filtering blebs on rabbit eyes. METHODS: Human Tenon's capsule fibroblasts were grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum and growth was measured with 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and direct counting of cell number. Production of collagen and transforming growth factor-beta 1 (TGF-beta 1) was measured with corresponding enzyme-linked immunosorbent assay (ELISA). In experimental filtering surgery performed on rabbit eyes, the effects of the topical drugs on intraocular pressure and on maintenance of the filtering blebs were observed. RESULTS: Both tranilast and ketotifen inhibited the growth of the fibroblasts and half-inhibitory concentrations were 200 microM and 70 microM, respectively. Low concentration (10 microM) of tranilast and ketotifen decreased the synthesis of collagen but neither drug had any obvious effect on TGF-beta 1 production. Both drugs prolonged the life of the experimental filtering bleb significantly [12.5 +/- 3.2 (mean +/- standard deviation) days, 13.9 +/- 3.4 days, respectively; control, 10.5 +/- 2.4 days]. CONCLUSION: Tranilast and ketotifen inhibited the growth of human Tenon's capsule proliferation and are capable of maintaining experimental filtering blebs in rabbit eyes.