97th DOG Annual Meeting 1999
V687
TOPICAL APPLICATION OF METHOTREXATE (MTX) FOR INHIBITION OF B-FGF INDUCED CORNEAL ANGIOGENESIS
A. M. Joussen1, F. E. Kruse2, H. E. Völcker
Purpose: Methotrexate (MTX) is an folic acid antagonist, used in chemotherapeutic regiments. New therapeutic applications have been suggested since it can act as an immune-modulating drug in systemic rheumatoid disease and associated uveitis. This implicates its potency for inhibition of angiogenesis. We have investigated MTX for topical treatment of corneal angiogenesis induced by fibroblast growth factor (b- FGF).
Methods: Corneal angiogenesis was induced by use of a micropocket assay in NZW rabbits. Pellets containing 500ng bFGF in 2% Methyl cellulose were implanted 2,5 mm from the limbus. Treated eyes received 0,1 ml of a solution of 2mg/ml MTX applied in a viscous eye gel once daily. Vessel growth was compared to controls. Serum and aqueous levels of MTX were measured.
Results: Vessel growth originating from the limbus was observed from day 3 after surgery. Vascularized area on day 9 were increased to 12,02±8,3 mm2 in the controls and 2,4±2,2 mm2 in treated eyes (p< 0,001). Neither of the treated animals showed topical side effects such as epithelial defects to the MTX drops. MTX levels could not be proven in the serum of the treated animals, although there was a therapeutical level within the anterior chamber fluid. Long term observations were able to prove the antiangiogenic potency of topical MTX.
Conclusion: When given at a topical dose of 0,2 mg/d, MTX significantly reduced corneal angiogenesis induced by b-FGF. However treated animals still exhibited a limited neovascular response. The antiangiogenic mechanism might be due to a combination of inhibition of macrophage invasion in the early angiogenesis and inhibition of endothelial cell proliferation. The high levels in the aqueous fluid without systemic action may suggest a possible application for MTX in inflammation of the anterior segment or in wound healing as well as in prevention of excessive pterygium as an alternative to Mitomycin-C.
1 Augenklinik der RWTH Aachen,
2 Augenklinik der Universität Heidelberg
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