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: Jenny A G McKenzie, Marcus Fruttiger, Sabu Abraham, Clemens A K Lange, Jay Stone, Pranita Gandhi, Xiaomeng Wang, James Bainbridge, Stephen E Moss, John Greenwood
• Journal: The American journal of pathology (Am J Pathol) Vol. 180 Issue 1 Pg. 399-409 (Jan 2012) ISSN: 1525-2191 [Electronic] United States
• PMID: 22067912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adipokines
• Apelin
• Apln protein, mouse
• Apln protein, rat
• Intercellular Signaling Peptides and Proteins

Topics

• Adipokines
• Animals
• Apelin
• Choroidal Neovascularization (genetics, metabolism, physiopathology)
• Gene Expression
• Gene Silencing
• Intercellular Signaling Peptides and Proteins (genetics, metabolism, physiology)
• Mice
• Microvessels (metabolism)
• Mutation (genetics)
• Rats
• Retina
• Retinal Degeneration (genetics, metabolism, physiopathology)
• Retinal Telangiectasis (prevention & control)
• Retinal Vessels (metabolism)
• Up-Regulation