Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy. One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

中文翻译：

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在新血管性年龄相关性黄斑变性患者中，尤其是患有黄斑纤维化的患者，血浆脂质运载蛋白2的水平升高

以前，我们和其他人已报道患有新生血管性年龄相关性黄斑变性（nAMD）的患者中循环中性粒细胞数量增加。中性粒细胞明胶酶相关的脂蛋白（NGAL，也称为lipocalin-2，LCN2），一种重要的先天免疫介质，已知与无菌炎症介导的器官衰竭，纤维化，癌症进展和视网膜变性密切相关。这项研究调查了不同类型的nAMD中LCN2，基质金属蛋白酶9（MMP9）和LCN2 / MMP9复合物的血浆水平，并检查了这些水平是否与患者对抗VEGF治疗的反应性相关。174例nAMD患者，包括108例脉络膜新生血管（CNV），32例视网膜血管瘤增生（RAP），该病例对照研究共招募了23例息肉样脉络膜血管病变（PCV）和11例未分类患者，以及43例健康对照。58名nAMD患者患有黄斑纤维化，而110名患者则没有。在174名nAMD患者中，80例完全缓解，90例部分缓解，4例对抗VEGF治疗无效。nAMD患者的LCN2血浆水平（181.46±73.62 ng / ml）显着高于健康对照组（152.24±49.55 ng / ml，P = 0.047）。但是，根据年龄调整后，差异消失了。在nAMD患者中，血浆LCN2水平与年龄呈正相关（r = 0.29，P = 0.0002），而在健康对照者中则没有。nAMD患者的LCN2血浆水平也与循环中性粒细胞呈正相关（r = 0.34，p = 0。0007），但在健康对照组中则不然（r = 0.057，p = 0.77）。在年龄和循环中性粒细胞之间未发现相关性。对nAMD亚型的进一步分析发现，即使调整了年龄，黄斑纤维化患者的LCN2水平也显着升高。血浆LCN2水平与患者对抗VEGF治疗的反应性之间没有关系。在nAMD和对照之间，MMP9和LCN2 / MMP9复合物的血浆水平相当。我们的结果表明，nAMD中LCN2的血浆水平升高与衰老和循环中性粒细胞数量增加有关。我们的结果还表明，较高水平的LCN2可能会增加nAMD中黄斑纤维化的风险。对nAMD亚型的进一步分析发现，即使调整了年龄，黄斑纤维化患者的LCN2水平也显着升高。血浆LCN2水平与患者对抗VEGF治疗的反应性之间没有关系。在nAMD和对照之间，MMP9和LCN2 / MMP9复合物的血浆水平相当。我们的结果表明，nAMD中较高的LCN2血浆水平与衰老和循环中性粒细胞数量增加有关。我们的结果还表明，较高水平的LCN2可能会增加nAMD中黄斑纤维化的风险。对nAMD亚型的进一步分析发现，即使调整了年龄，黄斑纤维化患者的LCN2水平也显着升高。血浆LCN2水平与患者对抗VEGF治疗的反应性之间没有关系。在nAMD和对照之间，MMP9和LCN2 / MMP9复合物的血浆水平相当。我们的结果表明，nAMD中LCN2的血浆水平升高与衰老和循环中性粒细胞数量增加有关。我们的结果还表明，较高水平的LCN2可能会增加nAMD中黄斑纤维化的风险。在nAMD和对照之间，MMP9和LCN2 / MMP9复合物的血浆水平相当。我们的结果表明，nAMD中LCN2的血浆水平升高与衰老和循环中性粒细胞数量增加有关。我们的结果还表明，较高水平的LCN2可能会增加nAMD中黄斑纤维化的风险。在nAMD和对照之间，MMP9和LCN2 / MMP9复合物的血浆水平相当。我们的结果表明，nAMD中LCN2的血浆水平升高与衰老和循环中性粒细胞数量增加有关。我们的结果还表明，较高水平的LCN2可能会增加nAMD中黄斑纤维化的风险。