Purchase this article with an account.
R. Wen, L. Zhao, Y. Liu, Y. Li, Y. Song, J.S. Rudge, A.M. Laties, S.J. Wiegand; VEGF Trap Induces Significant Regression of Existing Choroidal Neovascularization (CNV) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5307.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:The exudative form of age–related macular degeneration (AMD) is a major cause of severe vision loss in people over 65 years old in the western world. It is characterized by CNV with devastating consequences. Although prevention of CNV has been demonstrated to some degrees by a variety of agents, it would be of great clinical significance if regression of existing CNV could be induced. The present work investigates whether blocking VEGF by VEGF Trap, a potent soluble VEGF receptor composed of ligand–binding portions of human VEGFR–1 and VEGFR–2 fused to the Fc segment of IgG1, could induce regression of neovascularization in a subretinal Matrigel model of CNV. Methods:Sprague–Dawley rats (2.5 months old) were injected with Matrigel into the subretinal space. The first group of animals (10D control) received no treatment and were sacrificed 10D after Matrigel injection. VEGF Trap (12.5 mg/kg) or an equimolar concentration of a control protein (human Fc, 6.25 mg/kg) was delivered subcutaneously to the rest of the animals on days 10, 13, and 16 after Matrigel injection. The VEGF Trap and Fc treated groups were killed on day 20 (20D) after Matrigel injection. Animals were perfused with a DiI solution to stain blood vessels. Eyes were harvested and serial sections (100 µm each) covering the entire Matrigel–injected area were cut on a Vibratome and examined by fluorescence microscopy. The maximal width (W) of the CNV network in each section was measured (in µm) and the CNV index (C) was calculated by multiply W with the thickness of the section T (100 µm). The sum of CNV indexes of all the sections from an eye was taken as the CNV index of the eye. Student’s t test was used to evaluate the difference of CNV indexes between the 10D control and each treated group. Results:The CNV index for the 10D controls is 244,500±225,208 (Mean±SD) (n=16). The index for the VEGF Trap group is 37,097±45,868 (n=14), 15% of the 10D baseline (p=0.002). For the 20D Fc group, the index is 1,274,266±807,179 (n=14), 512% of the 10D control (p<0.0001). It should be noted that CNV was completely absent in 6 eyes among the 14 eyes of the VEGF Trap treated group. Conclusions:VEGF Trap treatment not only completely prevented the tremendous growth of CNV from 10D to 20D, but also induced regression of CNV to a level significantly below the 10D baseline. These findings demonstrated the importance of VEGF in CNV development and maturation. They also raise the possibility that newly formed blood vessels within CNV may be regressed by treatment with VEGF blockers like VEGF Trap.
This PDF is available to Subscribers Only