The role of the apelin/APJ pathway in retinal vascular development and pathology. (360G-Wellcome-091886_Z_10_Z)

In an attempt to gain a greater insight into the biological basis of retinal vascular pathology we have conducted a preliminary study to identify candidate genes that may contribute to the vascular changes that occur in various rodent models of retinal disease. This study revealed a significant increase in the expression of the small secreted peptide apelin and its cognate receptor APJ. The aim of this proposal is to investigate, using both in vivo and in vitro approaches, the role of the apelin /APJ pathway in driving the vascular changes observed in these different models of retinal disease and to determine in detail the retinal phenotype in the apelin knockout mouse. We aim to identify the key retinal cell sources of apelin, the factors that regulate apelin and APJ expression in these retinal cells. We will elucidate the signalling pathways mediated by apelin/APJ in endothelial cells and determine whether there is cross-talk with VEGF and/or Norrin/frizzled4/Lrp5 signalling pathways. The effect of modulating these pathways on endothelial cell function will be evaluated. These studies will define the role of the apelinergic system in retinal endothelial cell function in the context of vascular development and pathology.