Alterations in protein tyrosine kinase pathways following retinal vein occlusion in the rat

Abstract

Purpose. To determine whether an experimental retinal vein occlusion in the rat activates protein tyrosine kinase pathways and increases angiogenic growth factors in the retina. Methods. Retinal vein occlusion (RVO) was induced in the rat retina with argon laser photocoagulation. Retinas were collected at 2 days, 1, 2, and 4 weeks after RVO and divided into halves: one half represented an area within the distribution of the occluded vein [RVO(IN)] and the other half represented an area outside the distribution of the occluded vein [RVO(OUT)]. RVO(IN) and (OUT) were examined by western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and 3 signal proteins in the tyrosine kinase pathways: phospholipase C? (PLC?), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). Results. RVO caused a severe capillary nonperfusion in RVO(IN). Overall tyrosine-phosphorylated proteins were increased after RVO, especially in RVO(IN) at 2 days and 1 week. VEGF and bFGF were markedly increased in RVO(IN) at 2 days and 1 week. Tyrosine-phosphorylated PLC?, PI3K, and MAPK were also increased in RVO(IN) at these time points. Conclusions. RVO caused an increase in overall protein tyrosine phosphorylation in the rat retina. This increase was associated with an increase in angiogenic growth factors (VEGF and bFGF). These results suggest that protein tyrosine kinase pathways are activated during retinal ischemia and may play a role in mitogenesis of vascular endothelial cells and other responses in the retina after RVO.