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Apelin Is Required for Non-Neovascular Remodeling in the Retina

McKenzie, JA; Fruttiger, M; Abraham, S; Lange, CA; Stone, J; Gandhi, P; Wang, X; ... Greenwood, J; + view all (2012) Apelin Is Required for Non-Neovascular Remodeling in the Retina. The American Journal of Pathology , 180 (1) pp. 399-409. 10.1016/j.ajpath.2011.09.035. Green open access

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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.

Type: Article
Title: Apelin Is Required for Non-Neovascular Remodeling in the Retina
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajpath.2011.09.035
Publisher version: http://dx.doi.org/10.1016/j.ajpath.2011.09.035
Language: English
Additional information: © 2012. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0.
Keywords: Animals, Choroidal Neovascularization, Gene Expression, Gene Silencing, Intercellular Signaling Peptides and Proteins, Mice, Microvessels, Mutation, Rats, Retina, Retinal Degeneration, Retinal Telangiectasis, Retinal Vessels, Up-Regulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1331820
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