成纤维细胞生长因子21给药可抑制小鼠视网膜和脉络膜新生血管形成。
FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice.
作者信息
Fu Zhongjie, Gong Yan, Liegl Raffael, Wang Zhongxiao, Liu Chi-Hsiu, Meng Steven S, Burnim Samuel B, Saba Nicholas J, Fredrick Thomas W, Morss Peyton C, Hellstrom Ann, Talukdar Saswata, Smith Lois E H
机构信息
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Ophthalmology, Sahlgrenska Academy at University of Gothenburg, 413 90 Gothenburg, Sweden.
出版信息
Cell Rep. 2017 Feb 14;18(7):1606-1613. doi: 10.1016/j.celrep.2017.01.014.
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.
病理性血管生成是导致失明的主要原因，见于早产儿视网膜病变、糖尿病视网膜病变和年龄相关性黄斑变性。利用缺氧驱动的视网膜新生血管小鼠模型，我们发现给予成纤维细胞生长因子21（FGF21）可抑制视网膜新生血管生长，而FGF21缺乏则会使其恶化。在脂联素（APN）缺乏的小鼠中，FGF21对新生血管生长的保护作用消失。FGF21给药还减少了两种年龄相关性黄斑变性新生血管模型中的新生血管病变：患有视网膜血管瘤样增殖的极低密度脂蛋白受体缺陷小鼠和激光诱导的脉络膜新生血管。FGF21抑制肿瘤坏死α（TNF-α）表达，但不改变新生血管眼中Vegfa的表达。这些数据表明，FGF21可能是包括早产儿视网膜病变、糖尿病视网膜病变和年龄相关性黄斑变性在内的新生血管性眼病患者病理性血管生长的治疗靶点。
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