[Effect of anti-TNF-alpha on laser-induced choroidal neovascularization].
OBJECTIVE
To investigate the role of TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in the mouse.


METHODS
Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice by making four separate choroidal bums in each eye. Animals were treated 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept, 5 microg/h, group 1, n = 12), chimeric monoclonal antibody (infliximab, 5 microg/h, group 2, n = 12) for 7 days by intraperitoneally implanted osmotic pumps. PBS was used as control (group 3, n = 12). The left eyes were removed for histopathologic examination and the right eyes were removed for flatmounts immunohistochemistry immediately after fluorescein angiography. In mice treated with medications 3 days before laser injury, left eyes were collected at 1 or 2 weeks after laser injury. In mice treated with medications 3 days after laser injury, left eyes were collected at 10 days after laser injury. CNV responses were compared by flatmount analysis of CNV-related fluorescence area and by determination of fluorescein angiographic leakage. The level of protein expression of TNF-alpha was semiquantitatively evaluated by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment.


RESULTS
Western blotting demonstrated that TNF-alpha was highly expressed in choroidal and RPE cells of wild type mice 1 week after laser treatment as compared to the control mice without laser treatment. Etanercept and infliximab administrated 3 days before laser-damage significantly reduced CNV size and pathological fluorescein leakage in comparison to the control group one and two weeks after laser injury. Only etanercept administered 3 days after laser injury still significantly reduced the development of CNV lesions. Histopathological examination confirmed that CNV lesions in treated mice had smaller diameter and thinner center as compared to the control animals.


CONCLUSIONS
Anti-TNF-alpha treatment reduces the size and leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age related macular degeneration.
Shi
Xuan
X
Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China. xuanshi@yahoo.com
Semkova
Irina
I
Kociok
Norbert
N
Gavranic
Claudia
C
Becker
Martina
M
Joussen
Antonia M
AM
Kirchhof
Bernd
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000517:prevention & control*; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D000069285:Infliximab; D017075:Laser Coagulation / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D004656:Enalapril; D000069285:Infliximab