FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice

Publication date: 14 February 2017
Source:Cell Reports, Volume 18, Issue 7
Author(s): 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
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.

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Teaser

Fu et al. find that FGF21 administration suppresses pathological ocular blood vessel growth in the retina and choroid. The inhibitory effects depend on adiponectin and TNF-α but are independent of VEGFA.


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