This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosenbaum, J. T. Articles by Samples, J. R. Search for Related Content PubMed PubMed Citation Articles by Rosenbaum, J. T. Articles by Samples, J. R.

American Journal of Pathology, Vol 133, 47-53, Copyright © 1988 by American Society for Investigative Pathology

REGULAR ARTICLES

Ocular inflammatory effects of intravitreally-injected tumor necrosis factor

JT Rosenbaum, EL Howes Jr, RM Rubin and JR Samples
Oregon Health Sciences University, Portland 97201.

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.

This article has been cited by other articles:

				K. Kimura, S. Teranishi, K. Fukuda, K. Kawamoto, and T. Nishida Delayed Disruption of Barrier Function in Cultured Human Corneal Epithelial Cells Induced by Tumor Necrosis Factor-{alpha} in a Manner Dependent on NF-{kappa}B Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 565 - 571. [Abstract] [Full Text] [PDF]

				S. Biester, C. Deuter, H. Michels, R. Haefner, J. Kuemmerle-Deschner, D. Doycheva, and M. Zierhut Adalimumab in the therapy of uveitis in childhood Br. J. Ophthalmol., March 1, 2007; 91(3): 319 - 324. [Abstract] [Full Text] [PDF]

				X.-H. Jin, K. Ohgami, K. Shiratori, Y. Suzuki, T. Hirano, Y. Koyama, K. Yoshida, I. Ilieva, K. Iseki, and S. Ohno Inhibitory effects of lutein on endotoxin-induced uveitis in lewis rats. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2562 - 2568. [Abstract] [Full Text] [PDF]

				Y. Takamura, N. Fatma, E. Kubo, and D. P. Singh Regulation of heavy subunit chain of {gamma}-glutamylcysteine synthetase by tumor necrosis factor-{alpha} in lens epithelial cells: role of LEDGF/p75 Am J Physiol Cell Physiol, February 1, 2006; 290(2): C554 - C566. [Abstract] [Full Text] [PDF]

				J.-L. Hao, K. Suzuki, Y. Lu, S. Hirano, K. Fukuda, N. Kumagai, K. Kimura, and T. Nishida Inhibition of Gap Junction-Mediated Intercellular Communication by TNF-{alpha} in Cultured Human Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1195 - 1200. [Abstract] [Full Text] [PDF]

				G. Alexander, H. Carlsen, and R. Blomhoff Strong In Vivo Activation of NF-{kappa}B in Mouse Lenses by Classic Stressors Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2683 - 2688. [Abstract] [Full Text] [PDF]

				K. Koizumi, V. Poulaki, S. Doehmen, G. Welsandt, S. Radetzky, A. Lappas, N. Kociok, B. Kirchhof, and A. M. Joussen Contribution of TNF-{alpha} to Leukocyte Adhesion, Vascular Leakage, and Apoptotic Cell Death in Endotoxin-Induced Uveitis In Vivo Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2184 - 2191. [Abstract] [Full Text] [PDF]

				K. Ohta, K. Nakayama, T. Kurokawa, T. Kikuchi, and N. Yoshimura Inhibitory Effects of Pyrrolidine Dithiocarbamate on Endotoxin-Induced Uveitis in Lewis Rats Invest. Ophthalmol. Vis. Sci., March 1, 2002; 43(3): 744 - 750. [Abstract] [Full Text] [PDF]

				A. Yoshida, S. G. Elner, Z.-M. Bian, S. L. Kunkel, N. W. Lukacs, and V. M. Elner Differential Chemokine Regulation by Th2 Cytokines during Human RPE-Monocyte Coculture Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1631 - 1638. [Abstract] [Full Text]

				M. S. Lacomba, C. M. Martin, R. R. Chamond, J. M. G. Galera, M. Omar, and E. C. Estevez Aqueous and Serum Interferon {gamma}, Interleukin (IL) 2, IL-4, and IL-10 in Patients With Uveitis Arch Ophthalmol, June 1, 2000; 118(6): 768 - 772. [Abstract] [Full Text] [PDF]

				B. E. Brito, L. M. O’Rourke, Y. Pan, J. Anglin, S. R. Planck, and J. T. Rosenbaum IL-1 and TNF Receptor-Deficient Mice Show Decreased Inflammation in an Immune Complex Model of Uveitis Invest. Ophthalmol. Vis. Sci., October 1, 1999; 40(11): 2583 - 2589. [Abstract] [Full Text] [PDF]

				O. Marie, B. Thillaye-Goldenberg, M.-C. Naud, and Yvonne de Kozak Inhibition of Endotoxin-Induced Uveitis and Potentiation of Local TNF-{alpha} and Interleukin-6 mRNA Expression by Interleukin-13 Invest. Ophthalmol. Vis. Sci., September 1, 1999; 40(10): 2275 - 2282. [Abstract] [Full Text] [PDF]