title: The sustained delivery of resveratrol or a defined grape powder inhibits new blood vessel formation in a mouse model of choroidal neovascularization.
abstract: The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch's membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1666663111, Iran. rezaeikanavi@gmail.com.
authors.forename: Mozhgan Rezaie
authors.initials: MR
authors.lastname: Kanavi
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. srdarjat@wisc.edu.
authors.forename: Soesiawati
authors.initials: S
authors.lastname: Darjatmoko
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. shoujianwang@wisc.edu.
authors.forename: Shoujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Wills Eye Hospital, Philadelphia, PA 19107, USA. amirazarimd@gmail.com.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Azari
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. farnoodian@wisc.edu.
authors.forename: Mitra
authors.initials: M
authors.lastname: Farnoodian
authors.affiliation: Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602, USA. jason_kenealey@byu.edu.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Kenealey
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. prvangin@wisc.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: van Ginkel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. dalbert@wisc.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Albert
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. nsheibanikar@wisc.edu.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 USA. aspolans@wisc.edu.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Polans
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D016570:Bruch Membrane / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011208:Powders / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D015815:Cell Adhesion Molecules; D003692:Delayed-Action Preparations; D011208:Powders; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol