N-CAM Exhibits a Regulatory Function in Pathological Angiogenesis in Oxygen Induced Retinopathy

BackgroundDiabetic retinopathy and retinopathy of prematurity are diseases caused by pathological angiogenesis in the retina as a consequence of local hypoxia. The underlying mechanism for epiretinal neovascularization (tuft formation), which contributes to blindness, has yet to be identified. Neural cell adhesion molecule (N-CAM) is expressed by Müller cells and astrocytes, which are in close contact with the retinal vasculature, during normal developmental angiogenesis.
Methodology/Principal FindingsNotably, during oxygen induced retinopathy (OIR) N-CAM accumulated on astrocytes surrounding the epiretinal tufts. Here, we show that N-CAM ablation results in reduced vascular tuft formation due to reduced endothelial cell proliferation despite an elevation in VEGFA mRNA expression, whereas retinal developmental angiogenesis was unaffected.
Conclusion/SignificanceWe conclude that N-CAM exhibits a regulatory function in pathological angiogenesis in OIR. This is a novel finding that can be of clinical relevance in diseases associated with proliferative vasculopathy.

背景：糖尿病视网膜病变与早产儿视网膜病变均为局部缺氧引发视网膜病理性血管生成所致的疾病。可导致失明的视网膜前新生血管形成（即簇状结构生成，epiretinal neovascularization (tuft formation)）的潜在机制目前尚未阐明。在正常发育性血管生成过程中，神经细胞黏附分子（Neural cell adhesion molecule, N-CAM）由与视网膜血管系统紧密接触的米勒胶质细胞（Müller cells）与星形胶质细胞表达。

方法与主要发现：值得注意的是，在氧诱导视网膜病变（oxygen induced retinopathy, OIR）模型中，N-CAM会在视网膜前血管簇周围的星形胶质细胞上聚集。本研究证实，尽管VEGFA mRNA的表达水平升高，但敲除N-CAM可通过降低内皮细胞增殖，减少血管簇的形成，而视网膜发育性血管生成并未受到影响。

结论与意义：综上，N-CAM在氧诱导视网膜病变的病理性血管生成过程中发挥调控功能。这一全新发现可为增殖性血管病变相关疾病的临床诊疗提供潜在参考价值。