Purchase this article with an account.
Nina J. Jonsson, Gisela Weskamp, Krzysztof Glomski, Steven L. Swendeman, Rama Khokha, Carl P. Blobel; Pathological Retinal Neovascularization In Oxygen-induced Retinopathy Is Increased In Timp3-/- Mice, And Inhibited By Intravitreal Injection Of Erlotinib. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2548.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Pathological neovascularization is causal for the development of proliferative retinopathies. Previous studies have shown that pathological neovascularization is reduced by inactivation of ADAM17, which is important for EGFR signaling by cleaving and activating several EGFR-ligands. The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a natural inhibitor of ADAM17. In this study we investigated whether intravitreal injection of the EGFR-inhibitor Erlotinib (Tarceva®), an EGFR antagonist, inhibits pathological neovascularization after oxygen-induced retinopathy (OIR). Moreover, we tested how the lack of TIMP3 affected retinal neovascularization in mice following OIR.
Wild-type mice and Timp-3-/- mice underwent OIR (75% oxygen for 5 days starting at postnatal day 7 (P7), followed by 21% oxygen for additional 5 days). On P12 wild-type mice underwent a single intravitreal injection (0.5µl) of Erlotinib (20µM) or carrier control. The central avascular area and the development of neovascular tufts were measured at P17.
Mice injected with Erlotinib developed fewer neovascular tufts above the internal limiting membrane when compared to the untreated eye of a littermate, but vessel re-growth into the avascular area was not affected. Timp-3-/- mice showed greater revascularization and development of more neovascular tufts above the internal limiting membrane.
These studies demonstrate that Erlotinib is able to inhibit pathological neovascularization in mouse retina, most likely due to inactivation of the EGFR. These studies also suggest that TIMP-3 is a natural negative regulator of pathological neovascularization. Erlotinib, and potentially also TIMP3, could be used as anti-angiogenic compounds to prevent proliferative retinopathies.
This PDF is available to Subscribers Only