Purchase this article with an account.
S.G. Elner, V.M. Elner, A. Yoshida, R.D. Dick, G.J. Brewer; Effects of Tetrathiomolybdate on a Mouse Model of Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2004;45(13):482.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:To determine the effects of tetrathiomolybdate (TM), a copper chelating agent, on the development of retinal neovascularization and retinal production of vascular endothelial growth factor (VEGF) in a mouse model of retinopathy. Methods:One–week–old C57BL/6N mice (post–natal day [P7]) were exposed to 75% + 2% oxygen for 5 days (P12–P17) and then were retuned to room air to induce retinal neovascularization. Animals were either treated with daily intraperitoneal TM injections beginning on P10 or P12 and continued through P17. Control animals received phosphate buffered saline instead of TM. Retinal neovascularization was examined by injecting fluorescein dextran and angiography after 5 days in room air and was quantitated histologically by counting the endothelial cell nuclei anterior to the inner limiting membrane (ILM) in a masked protocol. The effects TM on retinal VEGF production were measured by ELISA. Results: Retinas from P17 mice injected with PBS (PBS controls) contained prominent neovascular tufts at the junction between the perfused and non–perfused retina, whereas P17 retinas from animals treated with TM demonstrated markedly reduced neovascular tissue despite the presence of comparable pericentral regions of non–perfusion. Retinas from PBS controls, contained large numbers of nuclei anterior to the ILM. Retinas from mice treated with TM beginning on P12 demonstrated no significant differences in the number of cell nuclei anterior to the ILM compared to PBS controls. However, retinas from mice treated with TM beginning on P10, 2 days prior to returning to room air, demonstrated fewer pre–retinal neovascular tufts, significantly fewer (p<0.01) endothelial cell nuclei anterior to the ILM, and significantly lower (P<0.01) levels of VEGF (140 + 22 pg/ml) compared to PBS controls (194 + 26 pg/ml). Conclusions:We have shown that TM significantly reduces the development of retinal neovascularization in a mouse model of retinopathy and that the inhibition of retinal neovascularization, at least in part, may be the result of inhibition of VEGF production by TM.
This PDF is available to Subscribers Only