title: Apelin is required for non-neovascular remodeling in the retina.
abstract: Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up-regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non-neovascular remodeling.
authors: Department of Cell Biology, University College London Institute of Ophthalmology, London, United Kingdom.
authors: Jenny A G
authors: JA
authors: McKenzie
authors: Marcus
authors: M
authors: Fruttiger
authors: Sabu
authors: S
authors: Abraham
authors: Clemens A K
authors: CA
authors: Lange
authors: Jay
authors: J
authors: Stone
authors: Pranita
authors: P
authors: Gandhi
authors: Xiaomeng
authors: X
authors: Wang
authors: James
authors: J
authors: Bainbridge
authors: Stephen E
authors: SE
authors: Moss
authors: John
authors: J
authors: Greenwood
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D055806:Microvessels / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D051381:Rats; D012160:Retina; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D058456:Retinal Telangiectasis / Q000517:prevention & control; D012171:Retinal Vessels / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; C498579:Apln protein, rat; D036341:Intercellular Signaling Peptides and Proteins