P 231Inhibition of inflammatory angiogenesis by tnp-470
A. M. Joussen1,2, Y. Moromizatol" W.-D. Beecken1, A. P. Adamis1,
Purpose: To determine the efficacy of the angiogenic inhibitor TNP- 470 on inflammatory corneal neovascularisation in a mouse model. Topica1 and systemica1 treatments were investigated as well as in vivo inhibition of proliferation.
Methods: The effect of TNP-470 on VEGF and bFGF stimulated bovine capillary endothelia1 cel1 (BCE) proliferation was eva1uated in vitro. A mouse in vivo-model of inflammatory cornea1 angiogenesis was used. TNP-470 was administered systemica1ly at 3Omg/kg BW every other day. For topica1 treatment TNP-470 was dissolved in methylcel1ulose and applied three times daily in a concentration of 5ng/ml. VEGF levels were ana1yzed by semiquantitative PCR. In vivo quantification of endothelia1 cel1 proliferation was performed by BrdU labeling.
Results: In vitro proliferation assays using bFGF and VEGF as wel1 as a combination of both revea1ed a dose dependent inhibition of proliferation. Systemic as wel1 as topica1 teatment with TNP-470 led to a significant reduction of inflamrnatory comea1 neovascularisation (P<0.05). In vivo BrdU labeling of endothelia1 cel1s showed inhibition of proliferation by TNP-470. VEGF gene expression was reduced by systemic TNP treatment.
Conclusion: These results suggest that TNP-470 is able to reduce inflammatory cornea1 angiogenesis by inhibtion of endothelia1 proliferation. The expression of VEGF associated with inflammatory comea1 angiogenesis was also significantly reduced by TNP treatment.
1Children's Hospital, Harvard Medical School,Boston MA, USA