| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Wound Healing Research Unit, Institute of Ophthalmology, London, United Kingdom; the 2 Glaucoma Unit, Moorfields Eye Hospital, London, United Kingdom; and the 3 Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, United Kingdom.
PURPOSE. To examine the effect of mitomycin-C on the expression of apoptosis genes in human Tenon capsule fibroblasts and to evaluate whether death receptor signaling modulates mitomycin-C cytotoxicity.
METHODS. Bcl-2, Bax, Bcl-x, Fas (CD95) and tumor necrosis factor (TNF) receptor
expression was determined by flow cytometry in control and
mitomycin-C–treated Tenon fibroblasts. Fibroblast death was quantified
using a lactate dehydrogenase release assay. The effect of Fas and
TNF-receptor signaling was evaluated using Fas-specific antibodies and
soluble TNF-
.
RESULTS. Tenon fibroblasts constitutively express Bcl-2, Bax, and Bcl-x in culture. Mitomycin-C (0.4 mg/mL) induced a small but consistent increase in the expression of all three proteins. Tenon fibroblasts express low levels of Fas but are resistant to the effects of Fas-receptor ligation. Mitomycin-C (0.01–1.0 mg/mL) led to a significant increase in Fas expression at all concentrations tested (P < 0.01). Pretreatment with mitomycin-C (0.4 mg/mL) rendered fibroblasts susceptible to agonistic anti-Fas monoclonal IgM antibodies (50–500 ng/mL) and led to a further 50% reduction in viable fibroblasts at 48 hours, compared with mitomycin-C alone (P < 0.05). Antibodies that block the Fas receptor did not inhibit mitomycin-C–induced apoptosis.
CONCLUSIONS. Mitomycin-C alters apoptosis gene expression and primes fibroblasts to the effects of Fas receptor ligation. Factors other than the level of Fas receptor expression modulate the response to Fas receptor signaling. Determining the signals that regulate fibroblast apoptosis may help to refine therapeutic strategies for switching off the subconjunctival healing response and maintaining intraocular pressure control.
This article has been cited by other articles:
|
|
 |
|
  X. Y. Wang, J. G. Crowston, H. Zoellner, and P. R. Healey Interferon-{alpha} and Interferon-{gamma} Sensitize Human Tenon Fibroblasts to Mitomycin-C Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3655 - 3661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Crowston, X. Y. Wang, P. T. Khaw, H. Zoellner, and P. R. Healey Human Serum Reduces Mitomycin-C Cytotoxicity in Human Tenon's Fibroblasts. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 946 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Seong, C. Park, C. Y. Kim, Y. J. Hong, H.-S. So, S.-D. Kim, and R. Park Mitomycin-C Induces the Apoptosis of Human Tenon's Capsule Fibroblast by Activation of c-Jun N-Terminal Kinase 1 and Caspase-3 Protease Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3545 - 3552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. L. Wong, A. L. Mead, and P. T. Khaw Prolonged Antiscarring Effects of Ilomastat and MMC after Experimental Glaucoma Filtration Surgery Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2018 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K T M Johnson, F Rodicker, K Heise, C Heinz, K-P Steuhl, B M Putzer, and T Hudde Adenoviral p53 gene transfer inhibits human Tenon's capsule fibroblast proliferation Br. J. Ophthalmol., April 1, 2005; 89(4): 508 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J G Crowston, L H Chang, J T Daniels, P T Khaw, and A N Akbar T lymphocyte mediated lysis of mitomycin C treated Tenon's capsule fibroblasts Br. J. Ophthalmol., March 1, 2004; 88(3): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
