Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a
| Autor: | Ankush Madaan, Martine Blais, Emilie Picard, Zhuo Shao, Andreas Stahl, Pierre Lachapelle, Pierre Hardy, Sophie Tremblay, Joseph A. Mancini, Huy Ong, Lois E.H. Smith, Tang Zhu, Sylvain Chemtob, Karine Zaniolo, Przemyslaw Sapieha |
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| Přispěvatelé: | CHU Sainte Justine [Montréal], Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Hôpital Maisonneuve-Rosemont, McGill University = Université McGill [Montréal, Canada], University of Freiburg [Freiburg], Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Picard, Emilie, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada] |
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis [SDV]Life Sciences [q-bio] Growth hormone secretagogue receptor MESH: Insulin-Like Growth Factor I Cell Culture Techniques MESH: Rats Sprague-Dawley Retinal Neovascularization MESH: Animals Newborn MESH: Receptors Ghrelin Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine MESH: Animals Insulin-Like Growth Factor I Receptor Fluorescent Antibody Technique Indirect Receptors Ghrelin 0303 health sciences MESH: Oxidative Stress MESH: Infant Newborn digestive oral and skin physiology MESH: Retinopathy of Prematurity MESH: Enzyme-Linked Immunosorbent Assay Articles Ghrelin 3. Good health [SDV] Life Sciences [q-bio] Vascular endothelial growth factor A medicine.anatomical_structure Intravitreal Injections MESH: Endothelium Vascular MESH: Neovascularization Physiologic MESH: Oxygen hormones hormone substitutes and hormone antagonists Retinopathy medicine.medical_specialty MESH: Rats Blotting Western MESH: Ghrelin Neovascularization Physiologic 030209 endocrinology & metabolism Enzyme-Linked Immunosorbent Assay Biology 03 medical and health sciences MESH: Intravitreal Injections MESH: Retinal Vessels Internal medicine MESH: Cell Proliferation medicine MESH: Blotting Western MESH: Fluorescent Antibody Technique Indirect Animals Humans Retinopathy of Prematurity 030304 developmental biology Cell Proliferation Retina MESH: Retinal Neovascularization MESH: Cell Culture Techniques MESH: Humans MESH: Vascular Endothelial Growth Factor A Infant Newborn Retinal Vessels Retinal medicine.disease Rats Oxygen Disease Models Animal Oxidative Stress Endocrinology chemistry Animals Newborn Endothelium Vascular MESH: Disease Models Animal |
| Zdroj: | Investigative Ophthalmology & Visual Science Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2011, 52 (8), pp.5376. ⟨10.1167/iovs.10-7152⟩ |
| ISSN: | 1552-5783 0146-0404 |
| DOI: | 10.1167/iovs.10-7152⟩ |
| Popis: | 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. (Invest Ophthalmol Vis Sci. 2011;52:5376‐5386) DOI:10.1167/iovs.10-7152 |
| Databáze: | OpenAIRE |
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