title: FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice.
abstract: Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization. FGF21 inhibited tumor necrosis α (TNF-α) expression but did not alter Vegfa expression in neovascular eyes. These data suggest that FGF21 may be a therapeutic target for pathologic vessel growth in patients with neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raffael
authors.initials: R
authors.lastname: Liegl
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhongxiao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Chi-Hsiu
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Meng
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Burnim
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Saba
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Fredrick
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peyton C
authors.initials: PC
authors.lastname: Morss
authors.affiliation: Department of Ophthalmology, Sahlgrenska Academy at University of Gothenburg, 413 90 Gothenburg, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Hellstrom
authors.affiliation: Cardiometabolic Diseases, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: mumpi462@yahoo.com.
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lois.smith@childrens.harvard.edu.
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: FGF21; choroidal neovascularization; hypoxia; oxygen-induced retinopathy; retinal neovascularization