Crespo-Garcia Sergio, Reichhart Nadine, Wigdahl Jeffrey, Skosyrski Sergej, Kociok Norbert, Strauß Olaf, Joussen Antonia M
Experimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Freie Universität, Humboldt-University, the Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, Montréal, Canada.
Graefes Arch Clin Exp Ophthalmol. 2019 Oct;257(10):2179-2184. doi: 10.1007/s00417-019-04447-3. Epub 2019 Aug 26.
Netrin-4 (NTN4) is a protein that plays an important role in the regulation of angiogenesis in the pathological retina. Some evidences show that it can also have a role in inflammation and vascular stability. We will explore these questions in vivo in the mature mouse retina.
We created a NTN4 knockout that expresses EGFP in mononuclear phagocytes (CSFR1-positive cells) to track inflammation in vivo in the retina by scanning laser ophthalmoscopy (SLO). Fundus angiography permitted to study blood vessels. Retinal function was assessed with electroretinography (ERG).
Lack of NTN4 leads to an increased amount of amoeboid mononuclear phagocytes in the adult retina, and blood vessels displayed increased tortuosity when compared with the wildtype. Inner retina function also seemed affected in NTN4 null. Lack of NTN4 resulted in a higher persistence of hyaloid artery and spontaneous leakage in the adult retina. No differences were found regarding vessel bifurcation, vessel width, or vein/artery ratio.
These in vivo data show for the first time that lack of NTN4 induces changes in the retinal vascular phenotype in a non-pathological scenario. This evidence widens the role of NTN4 as a guidance cue in vascular remodeling.
Netrin-4（NTN4）是一种在病理性视网膜血管生成调节中起重要作用的蛋白质。一些证据表明，它在炎症和血管稳定性方面也发挥作用。我们将在成熟小鼠视网膜中进行体内研究以探讨这些问题。
我们构建了一种NTN4基因敲除小鼠，其在单核吞噬细胞（CSFR1阳性细胞）中表达EGFP，通过扫描激光检眼镜（SLO）追踪视网膜内的炎症。眼底血管造影用于研究血管。视网膜功能用电视网膜图（ERG）进行评估。
与野生型相比，缺乏NTN4导致成年视网膜中阿米巴样单核吞噬细胞数量增加，血管迂曲度增加。NTN4基因敲除小鼠的视网膜内层功能似乎也受到影响。缺乏NTN4导致成年视网膜中玻璃体动脉的持续存在时间更长且出现自发渗漏。在血管分支、血管宽度或静脉/动脉比率方面未发现差异。
这些体内数据首次表明，在非病理情况下，缺乏NTN4会诱导视网膜血管表型发生变化。这一证据拓宽了NTN4作为血管重塑引导信号的作用。
