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Impressum
Therapy of angioproliferative retinopathy with soluble VEGF- and Tie- 2- receptors in a mouse model
Boden K. T., 2Fiedler U., 2Marmé D., 1Hansen L. L., 1Agostini H. T.
1Universitäts-Augenklinik Freiburg, 2Klinik für Tumorbiologie Freiburg
Objective: To reduce the experimentally induced retinal neovascularisation
in a mouse modell, we tried to diminish the effective concentration of
VEGF or Angiopoietin by local application of soluble receptors. The aim
is to develop an alternative therapy of hypoxia induced retinopathy frequently
seen in diabetics, prematurely born infants or patients with retinal vein
occlusion.
Methods: Seven days old C57/Bl6J mice were incubated together with
their mother in a chamber with 75% oxygen for 5 days. After returning
to room air the relative hypoxia caused a proliferative retinopathy which
was treated by intravitreal injection in one eye of each animal either
with chimaric recombinant VEGFR-2 or Tie-2 at day 12 postpartum (pp) using
the other eye as control. The mice were perfused with dextran coupled
flourescein at day 17 pp. To quantify retinal neovascularisation flat-mounts
of the retina were prepared.
Results: The induced angioproliferative retinopathy increased to
a maximum at day 17 pp and decreased afterwards. Local treatment with
soluble VEGFR-2 in one eye reduced neovascularisation when compared to
the other eye receiving only control substance. Injection of soluble Tie-2
was less effective
Conclusion: It is possible to reduce retinal neovascularisation
by injection of soluble VEGF- or Angiopoietin-receptors in this mouse
model. In our experiments VEGF-reducing therapy seems to be more effective
than the reduction of Angiopoietin. This experimental model is suitable
to evaluate other anti-angiogenic substances by local or systemic application
and to study pathogenic aspects of retinal neovascularisation.