Prolonged Blockade of VEGF Family Members Does Not Cause Identifiable Damage to Retinal Neurons or Vessels

Abstract

Purpose: : Since VEGF may function as a survival factor for retinal neurons, its inhibition in treatment of retinal diseases may cause unintended retinal or choroidal damage. We investigated the effect on the retina and choroid of prolonged, efficient blockade of VEGF family members.

Methods: : Double transgenic (Tet/IRBP/sVEGFR1Fc) mice underwent induced expression in photoreceptors of soluble VEGF receptor 1 coupled to an Fc fragment of IgG1 (sVEGFR1Fc) by treatment with oral doxycycline for 7 months. Retinal and choroidal structure and function were evaluated.

Results: : Treatment of adult Tet/IRBP/sVEGFR1Fc mice with 2 mg/ml of doxycycline in drinking water resulted in high levels of the chimeric VEGF binding protein in the retina measured by ELISA. Mice with constant retinal expression of sVEGF1Fc for 7 months had normal electroretinograms, and normal retinal and choroidal ultrastructure including normal fenestrations in the choroicapillaris. They showed no significant difference from control mice in the number of retinal ganglion cell axons in optic nerve cross sections or in retinal levels of mRNA for 3 ganglion cell-specific genes measured by real time PCR.

Conclusions: : These data indicate that constant blockade of VEGF for up to 7 months has no discernable deleterious effects on the retina or choroid, and provide support for the safety of VEGF antagonists in the treatment of retinal diseases and choroidal.

Keywords: vascular endothelial growth factor • transgenics/knock-outs • retina