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S. Ueno, K. Yokoi, M. Matsuoka, E. Keshet, P. Campochiaro; Conditional Knockdown of VEGF Family Members in the Eye. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1754.
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In this study we sought to investigate the effect of efficient blockade of several VEGF family members in the retina and choroid for various durations.
The tetracycline-inducible promoter system was used to generate double transgenic mice with inducible expression of soluble VEGF receptor 1 coupled to an Fc fragment of IgG1 (sVEGFR1-Fc) in the retina (Tet/opsin/sVEGFR1-Fc and Tet/IRBP/sVEGFR1-Fc).
Treatment of adult Tet/opsin/sVEGFR1-Fc or Tet/IRBP/sVEGFR1-Fc mice with 2 mg/ml of doxycycline in drinking water resulted in high levels of sVEGFR1-Fc in the retina measured by ELISA. After 1 or 3 months of doxycycline treatment, there was no significant difference in ERG a- and b-wave amplitudes compared to untreated mice, and light microscopy showed no evidence of structural damage to the retina or choriocapillaris. Onset of expression at the time of rupture of Bruch’s membrane strongly suppressed CNV, but onset of expression after CNV was established did not cause regression.
Strong, continuous blockade of VEGF-A and related family members for up to 3 months in the retina and choroid did not cause identifiable loss of retinal function or structural changes identifiable by light microscopy. The effect on ultrastructure and more detailed analyses are pending, but these preliminary data suggest that VEGF family members are not essential survival factors for mature vascular and neuronal cells in the retina. The blockade of VEGF family members strongly suppressed CNV, but did not cause established CNV to regress. This model will provide valuable information regarding the effects of long-term blockade of VEGF signaling in the retina and choroid.
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