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Results for “Tenon Capsule”

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At least 109 records · Page 6Linked to original sources

PubMed2005

Mitomycin-C induces the apoptosis of human Tenon's capsule fibroblast by activation of c-Jun N-terminal kinase 1 and caspase-3 protease.

PURPOSE: To investigate whether mitochondrial dysfunction and mitogen-activated protein kinase family proteins are implicated in apoptotic signaling of human Tenon's capsule fibroblasts (HTCFs) by mitomycin-C. METHODS: Apoptosis was determined by Hoechst nuclei staining, agarose gel electrophoresis, and flow cytometry in HTCFs treated with 0.4 mg/mL mitomycin-C for 5 minutes. Enzymatic digestion of florigenic biosubstrate assessed the catalytic activity of caspase proteases, including caspase-3, caspase-8, and caspase-9. Phosphotransferase activity of c-Jun N-terminal kinase (JNK) 1 was measured by in vitro immune complex kinase assay using c-Jun(1-79) protein as a substrate. Mitochondrial membrane potential transition (MPT) was measured by flow cytometric analysis of JC-1 staining. RESULTS: Mitomycin-C (0.4 mg/mL) induced the apoptosis of HTCFs, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G(0)/G(1) fraction of cell cycle increase. The catalytic activity of caspase-3 and caspase-9 was significantly increased and was accompanied by cytosolic release of cytochrome c and MPT in response to mitomycin-C. Treatment with mitomycin-C resulted in the increased expression of Fas, FasL, Bad, and phosphorylated p53 and a decreased level of phosphorylated AKT. Treatment with mitomycin-C also increased the phosphotransferase activity and tyrosine phosphorylation of JNK1, whose inhibitor significantly suppressed the cytotoxicity of mitomycin-C. CONCLUSIONS: Mitomycin-C induced the apoptosis of HTCFs through the activation of intrinsic and extrinsic caspase cascades with mitochondrial dysfunction. It also activated Fas-mediated apoptotic signaling of fibroblasts. Furthermore, the activation of JNK1 played a major role in the cytotoxicity of mitomycin-C.

Antibiotics, Antineoplastic↗

PubMed1996

Immunolocalization of prolyl 4-hydroxylase in fibroblasts cultured from Tenon's capsule of humans.

BACKGROUND: The excessive accumulation of extracellular matrix (ECM) with the repopulation of fibroblasts may lead to an unsuccessful outcome of glaucoma filtering surgery. We examined the immunolocalization of ECM components and prolyl 4-hydroxylase, an enzyme involved in collagen biosynthesis, in cultured Tenon's capsule fibroblasts (TCFs) of humans to evaluate the production of ECM in the cells. METHODS: We used light microscopy to evaluate the immunolocalization of prolyl 4-hydroxylase and ECM components, collagen types I, III, and IV, cellular fibronectin, and laminin in TCFs. Ultrastructural localization of the enzyme was also evaluated by electron microscopy. RESULTS: Immunoreactivity with monoclonal antibodies against the alpha and beta subunits of the enzyme or with the polyclonal antibody against it was detected in the cytoplasm of the cells in a fine granular pattern, indicating its localization in the endoplasmic reticulum (ER). Immunoreactivity for the enzyme was detected in the cisternae of the ER on electron microscopy. Types I and III collagen reactivities were also observed in the cytoplasm in a fine granular pattern. Type IV collagen reactivity was present diffusely on the cell surface. The distribution of laminin reactivity in the cytoplasm resembled that of types I and III collagen. Cellular fibronectin reactivity was observed in the ECM in a reticular pattern. CONCLUSION: Prolyl 4-hydroxylase was located in the cisternae of the ER. TCFs produced a variety of ECM components in vitro. The results provide insight into the fibrotic process during scar formation at the site of a bleb following filtering surgery.

Aged↗

PubMed1996

The effects of growth factors on Tenon's capsule fibroblasts in serum-free culture.

This study was performed to develop and improve a completely defined in vitro ocular wound-healing model of fibroblast proliferation for glaucoma filtration surgery. This model is essential for the investigation of protein-sensitive drugs and cytokines. Tenon's capsule fibroblasts in their third passage were incubated overnight, washed free of serum, and fed defined media, Aim V or Clonetics FBM serum-free medium containing platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, or fibronectin at various dilutions and in combinations at optimum concentrations. Proliferation was measured by 3H-thymidine incorporation at 1, 3, and 7 days. Morphology was compared to controls fed Minimum Essential Medium + 10% serum. Single factors stimulated the greatest amount of thymidine uptake on day 3. Optimum concentrations were epidermal growth factor at 5 ng/ml, basic fibroblast growth factor at 10 ng/ml and platelet-derived growth factor at 20 ng/ml. Identical combinations of factors stimulated nearly twice the thymidine uptake in Clonetics medium as in Aim V. Epidermal growth factor activity was inhibited by either basic fibroblast growth factor or platelet-derived growth factor. Basic fibroblast growth factor and platelet-derived growth factor together produced a less than additive effect. The performance of either serum-free medium may be improved by the addition of basic fibroblast growth factor or platelet-derived growth factor. The optimum serum-free medium (Clonetics FBM) with growth factors was unable to stimulate proliferation as much as Minimum Essential Medium + 10% NBS, but was successful in maintaining viability during the 7 day test period.

Cell Division↗

PubMed1991

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.

Adult↗

PubMed1995

Pilot study on the effect of topical adrenergic medications on human Tenon's capsule fibroblasts in tissue culture.

Recent publications have suggested that the long term use of topical antiglaucoma medications may be detrimental to the outcome of trabeculectomy. In order to investigate this further, the effect of several adrenergic agents and a preservative on the proliferation and viability of human Tenon's capsule fibroblasts in tissue culture were examined. The following compounds were tested: adrenaline (Eppy 1% and pure adrenaline base 1%, Smith & Nephew Pharmaceuticals Ltd); dipivefrine hydrochloride (Propine 0.1% and pure dipivefrine hydrochloride 0.1% Allergan Ltd and Allergan Pharmaceuticals (Ireland) Ltd); benzalkonium chloride (pure benzalkonium chloride 0.01%, Sigma Chemical Company Ltd); the two adrenaline based preparations were also tested in the presence of an antioxidant. None of the tested compounds stimulated the proliferation of fibroblasts. The commercial products tested, their pure compounds, and the preservative all inhibited proliferation and had toxic effects on the cells. In the presence of antioxidant, commercial Eppy and pure adrenaline base appeared to have less effect on proliferation and toxicity. These findings are discussed with reference to the outcome of trabeculectomy.

Adrenergic Agents↗

PubMed1995

The effect of topical beta-blocker medications on the proliferation and viability of human Tenon's capsule fibroblasts in tissue culture.

Several recent publications have suggested that the long-term use of topical antiglaucoma medications may be detrimental to the outcome of trabeculectomy. In this study we investigated the effect of topical beta-blocker medications on the proliferation and viability of human Tenon's capsule fibroblasts in tissue culture to see if there was a direct mechanism of enhanced proliferation. None of the tested medications stimulated the proliferation of fibroblasts. They were shown to have an inhibitory effect on proliferation and were toxic to cells at higher concentrations. The relevance of these findings to wound healing following trabeculectomy is discussed.

Adrenergic beta-Antagonists↗

PubMed2000

Cytokine regulation of hyaluronate production by human Tenon's capsule fibroblasts.

PURPOSE: The high-molecular weight glycosaminoglycan hyaluronate (HA), a component of the extracellular matrix, has been shown to play important roles in many biological processes including cell proliferation, migration and differentiation. In the present study, the effect of cytokines on production of hyaluronate (HA) by human tenon's capsule fibroblasts (HTF) was determined. METHODS: HTF (2(nd) passage) were seeded at a cell density of 30 cells/mm(2) and stimulated by six different cytokines (platelet-derived growth factor (PDGF)-AA, PDGF-BB, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), interleukin (IL)-1beta and transforming growth factor (TGF)-beta1). Controls were treated with aliquots of serum-free medium only. Concentrations of HA were determined using a radiometric assay based on the specific binding of HA to HA binding proteins. RESULTS: The concentration of HA in conditioned medium of HTF was significantly increased only after stimulation with PDGF-AA [10 and 100ng/ml], IL-1beta [1 and 10ng/ml] and TGF-beta1 [5ng/ml]. CONCLUSIONS: Production of HA by HTF is regulated by PDGF-AA, IL-1beta and TGF-beta1 and is speculated to be involved in the wound healing reaction after glaucoma filtration surgery.

Becaplermin↗

PubMed2005

Adenoviral p53 gene transfer inhibits human Tenon's capsule fibroblast proliferation.

BACKGROUND/AIM: Although antiproliferative drugs have been used successfully to prevent scarring after filtration surgery in patients with glaucoma, complications associated with their use (such as hypotony or endophthalmitis) energise the search for an alternative treatment. Single application of beta radiation leads to long term growth arrest and expression of p53 in human Tenon's capsule fibroblasts (hTf). The authors assume that the activation of p53 is one of the cellular triggers. Their aim was to analyse the effect of p53 overexpression on hTf and to determine which pathways are involved. METHODS: A recombinant adenoviral vector (rAd.p53) containing transgenes encoding for human p53 and green fluorescent protein (GFP) was used to induce overexpression of p53 in hTF and a control vector (rAd.GFP). Transgene expression was detected by western blot (p53 and p21WAF-1/Cip1). Cell proliferation and viability were investigated using cell counts, 5'-bromodeoxyuridine incorporation (BrdU assay) and tetrazolium reduction (MTT assay). RESULTS: Infection of hTf with rAd.p53 resulted in significant inhibition of cell proliferation, DNA synthesis, and metabolic activity in vitro. Western blot showed increased levels of p53 and p21WAF-1/Cip1 in rAd.p53 infected cells, but not in rAd.GFP and uninfected cells. Apoptosis was excluded with flow cytometry. CONCLUSIONS: Adenoviral p53 gene transfer leads to significant growth inhibition in hTf. P53 induces p21(WAF-1/Cip1) expression and does not cause apoptosis in hTf in vitro. p53 as an antiproliferative drug has the potential to replace mitomycin C and 5-fluorouracil in glaucoma surgery.

Adenoviridae↗

PubMed1983

Epibulbar subconjunctival fibroma. A tumor possibly arising from Tenon's capsule.

A fibroma, a benign neoplasm arising from the periorbita or tendon sheaths, is described in a 74-year-old woman as an indolent, lobular tumor situated in the episcleral and subconjunctival connective tissues with superior limbal fixation. Because most fibromas arise from tendon sheaths or fascial planes, we speculate that our lesion arose from Tenon's capsule. The rarity of periocular fibroma is documented by a review of the modern ophthalmic literature. Histopathologically, the tumor was composed of a paucicellular population of fibroblasts, sometimes displaying hyperchromatic nuclei and widely separated by abundant broad bundles of collagen. Mast cells were infrequently dispersed in the lesion. A wide local excision was performed, and no recurrence has developed during an 18-month follow-up period.

Aged↗

PubMedDate not supplied

In vitro effect of ascorbic acid on the proliferation of bovine scleral and Tenon's capsule fibroblasts.

The success of glaucoma filtration surgery depends mainly on an incomplete wound healing process in the area of the fistula. Since Kornblueth and Tenenbaum's investigations in 1956 it has been known that aqueous humour has intrinsic antiproliferative properties. It is assumed that ascorbic acid is involved in the regulation of the wound healing process after filtration surgery. To evaluate the antiproliferative effect of ascorbic acid in vitro, we used cultured fibroblasts of bovine Tenon's capsule and bovine sclera. Incubation of these cells with ascorbic acid at concentrations ranging from 0.5 to 3 mM/L led to dose-dependent inhibition of cell proliferation. The half-maximal inhibitory concentration was 1.0 mM/L for both cell types. Physiological concentrations of ascorbic acid may be valuable in the pharmacological prevention of failure of glaucoma filtration surgery. However, extensive clinical investigations are needed to clarify whether topical intraoperative or postoperative as well as oral administration of ascorbic acid inhibits fibroblast proliferation after glaucoma filtration surgery.

Animals↗

PubMed1993

The effects of photofrin on human Tenon's capsule fibroblasts in vitro.

Pharmacological agents that modulate the wound healing process by inhibiting fibroblast proliferation may improve the success of proliferative vitreoretinopathy and glaucoma filtration surgery and may have applications in other surgical fields. It is possible that light-absorbing chemicals can be used to cause photo reactions in proliferating fibroblasts as a means of controlling this wound healing process. We present the effects of photofrin porfimer sodium (serial tenfold dilutions 1000-0.00001 micrograms/ml) on human fibroblasts from Tenon's capsule in vitro, with and without photoactivation with Argon green laser (700 mW for 1 and 5 minutes) and with bright sunlight (for 1 and 5 min). The cell density was measured on day 2 by 3H-thymidine uptake and on day 9 by means of a coulter counter, and optical density was measured in terms of the activity of the enzyme hexosaminidase. Each experiment was performed three times in quadruplicate. The counts were averaged for each drug concentration and mean cell count with a standard error as well as the 50% inhibitory doses (ID50s) were calculated. Photofrin demonstrated an inhibitory dose response curve (dark toxicity) to human fibroblasts. Concentrations greater than 100 micrograms/ml of photofrin alone completely inhibited cell growth. Concentrations less than 0.01 micrograms/ml did not have any effect on fibroblast proliferation. There was no significant log dose shift of the inhibitory effect of photofrin with the exposure to either sunlight or Argon laser. Photofrin may be used as a cytotoxic agent alone but does not appear to be activated by light to modulate subconjunctival fibroblast proliferation within the laser parameters used.

Cell Count↗

PubMed1990

Ascorbic acid is cytotoxic to dividing human Tenon's capsule fibroblasts. A possible contributing factor in glaucoma filtration surgery success.

Successful glaucoma filtration surgery depends on the incomplete healing of the surgical wound, with formation of a filtration bleb. In most other tissues, however, complete healing is the rule. I have explored the possibility that the high concentration of ascorbic acid normally present in aqueous humor inhibits wound healing after filtration surgery. At the concentration normally present in aqueous humor (1.1 mmol/L), ascorbic acid decreased the plating efficiency of cell suspensions of human Tenon's capsule fibroblasts by a mean (+/- SD) of 40% +/- 10%. When added to low-density monolayer cultures of fibroblasts, ascorbic acid decreased the cell number by 90% +/- 5%, an effect that was completely prevented by catalase. When added to confluent cultures, the cell number was decreased by only 14% +/- 2%. If ascorbic acid has similar effects on fibroblasts in vivo, it may contribute to the incomplete wound healing that characterizes successful glaucoma surgery.

Ascorbic Acid↗

PubMed1994

Transcriptional control of human Tenon's capsule fibroblast collagen synthesis in vitro by gamma-interferon.

PURPOSE: Gamma-interferon (gamma-IFN) has been shown to be a potent inhibitor of collagenous protein production independent of its effects on noncollagenous protein production and cell proliferation in vitro. To understand further the processes controlling tissue fibrosis and the potential use of gamma-IFN as an antifibrotic treatment after glaucoma filtering surgery, the in vitro effects of recombinant gamma-IFN on procollagen mRNA production were studied. METHODS: Subconfluent human Tenon's capsule fibroblast cultures were exposed to 10, 50, 500, and 1000 U/ml of human recombinant gamma-IFN for 48 hours and to 500 U/ml for 12, 24, and 72 hours. After the incubation period, polyA+ mRNAs were isolated by oligo (dT) cellulose columns, separated according to size by electrophoresis through a denaturing agarose gel, and transferred to an activated nylon membrane for Northern blot analysis. The levels of type III (alpha 1) procollagen, type I (alpha 1) procollagen, and fibronectin (noncollagenous protein) mRNA were determined by hybridization with radiolabeled cDNA probes specific for these components followed by autoradiography. RESULTS: Densitometric analysis showed gamma-IFN selectively inhibited type III and type I procollagen mRNA synthesis from 24% (10 U/ml) to 99% (1000 U/ml) while leaving fibronectin mRNA synthesis unaffected. The degree of inhibition was also time dependent; more inhibition occurred with increasing incubation time. CONCLUSIONS: These results indicate that gamma-IFN is able to regulate collagen synthesis at the transcriptional level and that its inhibition is relatively specific. Gamma-interferon's specific inhibitory effects may offer advantages over current therapies in modulating the fibrotic response after glaucoma filtering surgery.

Cell Line↗

PubMed1988

[Polyglactin 910 implants in muscle revision surgery for the reconstruction of physiologic limits in Tenon's capsule].

Iatrogenic damage to the orbital fascial system during strabismus surgery may lead to adherences with resulting problems of motility. To prevent new adherences in revisional surgery, several materials were tried, with varying degrees of success. The authors tested Polyglactin 910, popular as a suture material in strabismus surgery, in the form of a net. The material is hydrolytically soluble. Since the tissue response is finished before dissolution of the implant, it seemed that Polyglactin would be a suitable barrier to the formation of adhesions in Tenon's capsule. The implant was applied in 11 patients, some of whom had already undergone several strabismus operations and had adhesions at the surgical site. In one case the implant was used in a primary procedure. In one patient revisional surgery was needed four weeks after surgery because of overeffect, and this provided an opportunity to investigate the implanted area histologically.

Adolescent↗

PubMed1992

The effects of transferrin receptor antibody, transferrin receptor antibody bound to Pseudomonas exotoxin and transforming growth factor-alpha bound to Pseudomonas exotoxin on human tenon's capsule fibroblast proliferation.

Pharmacological agents which modulate the wound healing process by the inhibition of proliferation of fibroblasts may improve the success of glaucoma filtration surgery. Since cell proliferation is essential to the wound healing process, we targeted the surface receptors that are associated with proliferating cells. We present the effects of three such agents-purified mouse anti-human transferrin receptor monoclonal antibody 42/6 (anti-TfR-42/6), anti-transferrin monoclonal antibody bound to a Pseudomonas exotoxin (anti-TfR-PE40) and transforming growth factor-alpha Pseudomonas exotoxin (TGF-alpha-PE40)--on human fibroblasts from Tenon's capsule. The inhibition of human subconjunctival fibroblast proliferation by anti-TfR-42/6 (with a concentration up to 25 micrograms/ml) and by anti-TfR-PE40 and TGF-alpha-PE40 (both with a concentration range of 5000-0.00001 micrograms/ml) was determined by colorimetric (OD), and cell counting (CC) assays over a 9-day period. Neither anti-TfR-42/6 nor anti-TfR-PE40 had an antiproliferative effect on the fibroblasts. TGF-alpha-PE40 demonstrated an antiproliferative effect in a dose response manner. The mean 50% inhibitory dose (ID50) by OD was 32.91 micrograms/ml, while the ID50 by CC was 27.88 micrograms/ml. EGF was used as a negative control for TGF-alpha-PE40 toxin. The inhibitory effect of the toxin conjugate was completely blocked by the addition of 1000 micrograms/ml of EGF. These in vitro studies show that TGF-alpha-PE40 may be useful in modulating the proliferation of human ocular fibroblasts; they also give some indication of drug dosages for future in vivo testing.

ADP Ribose Transferases↗

PubMed1995

Effect of TNF, IL-1, and IL-6 on the proliferation of human Tenon's capsule fibroblasts in tissue culture.

Trabeculectomy is a commonly performed procedure for primary open angle glaucoma and is successful in the majority of cases. However, certain factors including aphakia, previous surgery, secondary glaucomas, ethnic origin, and the long term use of topical antiglaucoma medications may be associated with a reduced success rate. The mechanism (or mechanisms) which influence clinical outcome following trabeculectomy remain elusive. Alterations in the composition of the conjunctiva or aqueous humour may be partly responsible for this effect, and this could be mediated by cytokines. In this study we found that tumour necrosis factor (TNF), and interleukin 1 (IL-1) were capable of stimulating the proliferation of Tenon's capsule fibroblasts in tissue culture. Interleukin 6 (IL-6) did not appear to have any effect. The relevance of this to wound healing following trabeculectomy is discussed.

Aged↗

PubMed1976

Proplast implant in Tenon's capsule after excision of the eye.

Hitherto implants used after enucleation have generally been extruded because of infection or tissue rejection. Proplast, an inert alloplastic material prepared from a combination of Teflon fluorocarbon polymer and vitreous carbon fibres, is a grey felt-like material which, when wholly implanted, is invaded by fibrous tissue and not rejected. Hemispherical implants of Proplast have been used in sixteen cases, no rejection has occurred to date (18 months), and movement of the implant has been good. At operation, the obliques are sutured posterior to the implant so as to hold it forwards and increase movement. The rectus muscles are sutured anterior to the implant in cruciate fashion. Tenon's capsule and the conjunctiva are closed separately.

Carbon↗

PubMed1994

Growth inhibition of human Tenon's capsule fibroblasts and rabbit dermal fibroblasts with non-carcinogenic N-alkylated anthracyclines.

Bleb fibrosis after glaucoma filtering surgery and proliferative vitreoretinopathy after retinal detachment surgery are complications caused by proliferation of fibroblasts or fibroblastlike cells. The anthracycline daunomycin (DNM) has been used for treatment of those proliferative processes in humans. However, complications such as conjunctival necrosis and corneal or scleral ulcerations have been reported after administration of DNM to glaucoma patients. Intravitreal administration of DNM in rabbit eyes resulted in morphological and functional retinal damage. DNM also has the undesired general effect of carcinogenicity. N-Alkylation of the aminosugar moiety of DNM results in reduction or loss of carcinogenicity. We evaluated the inhibitory effect of the new non-carcinogenic N-alkylated analogues aclacinomycin A (ACA), N,N-dimethyladriamycin (AD280), and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143) on the growth of cultured human Tenon's capsule fibroblasts and rabbit dermal fibroblasts. Using DNM as a positive control, we conducted proliferation assays that demonstrated that ACA and AD280 inhibited fibroblast growth as effectively as DNM. AD143 was less efficacious. The magnitude of cellular growth inhibition was concentration dependent for all drugs tested. Extension of exposure times resulted in increased rates of cell death. Our in vitro studies suggest that further evaluation of ACA and AD280 should be carried out in animal models of ocular proliferative disorders.

Animals↗