FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice

Zhongjie Fu; Yan Gong; Raffael Liegl; Zhongxiao Wang; Chi-Hsiu Liu; Steven S. Meng; Samuel B. Burnim; Nicholas J. Saba; Thomas W. Fredrick; Peyton C. Morss; Ann Hellstrom; Saswata Talukdar; Lois E.H. Smith

doi:10.1016/j.celrep.2017.01.014

Cell Reports (Feb 2017)

FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice

Zhongjie Fu,
Yan Gong,
Raffael Liegl,
Zhongxiao Wang,
Chi-Hsiu Liu,
Steven S. Meng,
Samuel B. Burnim,
Nicholas J. Saba,
Thomas W. Fredrick,
Peyton C. Morss,
Ann Hellstrom,
Saswata Talukdar,
Lois E.H. Smith

Affiliations

Zhongjie Fu: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Yan Gong: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Raffael Liegl: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Zhongxiao Wang: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Chi-Hsiu Liu: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Steven S. Meng: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Samuel B. Burnim: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Nicholas J. Saba: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Thomas W. Fredrick: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Peyton C. Morss: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Ann Hellstrom: Department of Ophthalmology, Sahlgrenska Academy at University of Gothenburg, 413 90 Gothenburg, Sweden
Saswata Talukdar: Cardiometabolic Diseases, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
Lois E.H. Smith: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA

DOI: https://doi.org/10.1016/j.celrep.2017.01.014
Journal volume & issue: Vol. 18, no. 7
pp. 1606 – 1613

Abstract

Read online

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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords