Effect of intravitreal anti-vascular endothelial growth factor treatment on the retinal gene expression in acute experimental central retinal vein occlusion

Abstract

Purpose: To determine the effect of intravitreal bevacizumab and anti-vascular endothelial growth factor (VEGF) antibodies on the gene expression in the neural retina in a rat model of central retinal vein occlusion (CRVO).

Methods: The CRVO was induced by laser photocoagulation of all retinal veins. The animals were divided into 3 groups (in each, n = 16): group CRVO only without any further treatment, group CRVO with bevacizumab, and group CRVO with anti-VEGF antibodies. The intravitreal injection of bevacizumab or anti-VEGF antibodies was performed 15 min after CRVO induction. The left eyes in all animals served as untreated controls. The expression of factors which influence the development of vascular edema (VEGF-A, pigment epithelium-derived factor, PEDF), of channels implicated in retinal osmohomeostasis (Kir4.1, AQP4, AQP1) and of the proinflammatory cytokines interleukin (IL)-1β and IL-6 was determined by using real-time RT-PCR after 1 and 3 days of CRVO.

Results: CRVO induced a rapid transient upregulation of Vegfa after 1 day, and a delayed upregulation of Pedf after 3 days of CRVO. The expression levels of Kir4.1, Aqp4 and Aqp1 were strongly decreased, and the levels of Il1β and Il6 were strikingly increased after CRVO. Intravitreal bevacizumab and anti-VEGF antibodies fully prevented the upregulation of Vegfa after 1 day, and the upregulation of Pedf after 3 days of CRVO, and decreased the upregulation of Il1β after 1 day of CRVO. Anti-VEGF treatment had no effect on the expression levels of Kir4.1, Aqp4, Aqp1, and Il6.

Conclusions: It is suggested that the inhibitory effect on the upregulation of Vegfa and Il1β contributes to the edema-resolving effect of anti-VEGF treatment.