|
|
||||||||
1From the Department of Vitreoretinal Surgery, Center for Ophthalmology, and the 2Center for Molecular Medicine, University of Cologne, Cologne, Germany; and 3Department of Ophthalmology, Heinrich-Heine University, Düsseldorf, Germany.
PURPOSE. Tumor necrosis factor (TNF)-
is one of the major cytokines in inflammation and apoptosis. It has been demonstrated that inhibition of TNF
can reduce leukocyte adhesion, vascular leakage, and apoptotic endothelial cell death in diabetes. This study was conducted to investigate the effect of TNF-Rp55 and TNF-Rp75 on retinal development in oxygen-induced retinopathy.
METHODS. TNF-Rp55 and TNF-Rp75deficient mice, as well as their respective wild-type controls, were exposed to 75% oxygen from postnatal day P7 to P12. Retinal vascularization was investigated in flatmount preparations after concanavalin A labeling of endothelial cells on days P6, P14, P17, and P20. Retinal mRNA expression of VEGF, angiopoietin-1 and -2, and PDGF was examined at days P14 and P20.
RESULTS. TNF-Rp55 and TNF-Rp75deficient mice demonstrated similar retinal development and vascularization under normoxic conditions. In comparison to wild-type mice, the vascularized area remained stable during the observation time, although the gene expression of VEGF, angiopoietin (ang)-1 and -2, and PDGFb changed. Compared with that in the wild type mice, the relative expression of VEGF, ang-1, ang-2, and PDGFb changed 5.14-, 1.7-, 0.39-, and 0.36-fold in Rp55/ mice and 4.1-, 9.5 x 105-, 0.12-, and 2975-fold in Rp75/ mice, respectively. Treatment with oxygen resulted in a significantly reduced vascularization in Rp55/ but not Rp75/ mice on postnatal day (P)20.
CONCLUSIONS. Inhibition of TNF
via TNF-Rp55 can alter retinal development and angiogenesis in a model of oxygen-induced retinopathy. The data underscore the potential effectiveness of TNF-inhibitory treatments as modulators in oxygen-induced retinopathy.
This article has been cited by other articles:
![]() |
R. C. A. Sainson, D. A. Johnston, H. C. Chu, M. T. Holderfield, M. N. Nakatsu, S. P. Crampton, J. Davis, E. Conn, and C. C. W. Hughes TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype Blood, May 15, 2008; 111(10): 4997 - 5007. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |