Experimental Ophthalmology, Department of Ophthalmology, Charité-Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, Germany.
Department of Biochemistry, Hospital Maisonneuve-Rosemont Research Center, University of Montreal, 5415 Blvd. Assomption, Montreal, QC H1T 2M4, Canada.
Int J Mol Sci. 2021 Apr 25;22(9):4481. doi: 10.3390/ijms22094481.
Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin-4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membrane and highly expressed in the retina. A number of studies inferred that the angiogenic abilities of NTN4 could contribute to stabilize vascular networks and modulate inflammation. Analyzing human specimens, we show that and netrin receptors are upregulated in the diabetic retina. We further evaluated a knock-out model for NTN4 undergoing experimental diabetes induced by streptozotocin. We investigated retina function and immune cells in vivo and demonstrated that NTN4 provides a protective milieu against inflammation in the diabetic retina and prevents cytokine production.
糖尿病性视网膜病变的特征是视网膜血管网络功能障碍，伴有持续的低度炎症，导致威胁视力的并发症。轴突导向因子 4（NTN4）是一种层粘连蛋白相关的分泌蛋白和导向分子，存在于血管基底膜中，在视网膜中高度表达。一些研究推断，NTN4 的血管生成能力有助于稳定血管网络并调节炎症。通过分析人类标本，我们表明 和轴突导向因子受体在糖尿病视网膜中上调。我们进一步评估了 NTN4 敲除模型在链脲佐菌素诱导的实验性糖尿病中的作用。我们在体内研究了视网膜功能和免疫细胞，并证明 NTN4 为糖尿病视网膜中的炎症提供了一种保护环境，并防止细胞因子的产生。
