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Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a.

Authors: Zaniolo, Karine  Sapieha, Przemyslaw  Shao, Zhuo  Stahl, Andreas  Zhu, Tang  Tremblay, Sophie  Picard, Emilie  Madaan, Ankush  Blais, Martine  Lachapelle, Pierre  Mancini, Joseph  Hardy, Pierre  Smith, Lois E H  Ong, Huy  Chemtob, Sylvain 
Citation: Zaniolo K, etal., Invest Ophthalmol Vis Sci. 2011 Jul 23;52(8):5376-86. doi: 10.1167/iovs.10-7152.
Pubmed: (View Article at PubMed) PMID:21642627
DOI: Full-text: DOI:10.1167/iovs.10-7152

PURPOSE: Vascular degeneration and the ensuing abnormal vascular proliferation are central to proliferative retinopathies. Given the metabolic discordance associated with these diseases, the authors explored the role of ghrelin and its growth hormone secretagogue receptor 1a (GHSR-1a) in proliferative retinopathy.
METHODS: In a rat model of oxygen-induced retinopathy (OIR), the contribution of ghrelin and GHSR-1a was investigated using the stable ghrelin analogs [Dap3]-ghrelin and GHRP6 and the GSHR-1a antagonists JMV-2959 and [D-Lys3]-GHRP-6. Plasma and retinal levels of ghrelin were analyzed by ELISA, whereas retinal expression and localization of GHSR-1a were examined by immunohistochemistry and Western blot analysis. The angiogenic and vasoprotective properties of ghrelin and its receptor were further confirmed in aortic explants and in models of vaso-obliteration.
RESULTS: Ghrelin is produced locally in the retina, whereas GHSR-1a is abundantly expressed in retinal endothelial cells. Ghrelin levels decrease during the vaso-obliterative phase and rise during the proliferative phase of OIR. Intravitreal delivery of [Dap3]-ghrelin during OIR significantly reduces retinal vessel loss when administered during the hyperoxic phase. Conversely, during the neovascular phase, ghrelin promotes pathologic angiogenesis through the activation of GHSR-1a. These angiogenic effects were confirmed ex vivo in aortic explants.
CONCLUSIONS: New roles were disclosed for the ghrelin-GHSR-1a pathway in the preservation of retinal vasculature during the vaso-obliterative phase of OIR and during the angiogenic phase of OIR. These findings suggest that the ghrelin-GHSR-1a pathway can exert opposing effects on retinal vasculature, depending on the phase of retinopathy, and thus holds therapeutic potential for proliferative retinopathies.


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CRRD Object Information
CRRD ID: 12904963
Created: 2017-05-30
Species: All species
Last Modified: 2017-05-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.