Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2022 Jun 16;17(6):e0269960. doi: 10.1371/journal.pone.0269960. eCollection 2022.
Peripheral T cell CXCR3 expression has been found uniquely lower in patients having neovascular age-related macular degeneration (nAMD) than in healthy individuals. The CXCR3-axis has been shown to have angiostatic and antifibrotic properties. We have recently investigated systemic markers in patients with myeloproliferative neoplasms (MPNs) because of their higher prevalence of AMD, and we have observed higher systemic chronic low-grade inflammation and immunosenescence signs in MPNs with drusen (MPNd) compared to those with normal retinas (MPNn). The MPNs evolve in a biological continuum from early cancer-stages (essential thrombocytosis, polycythemia vera) to the advanced myelofibrosis stage. Especially myelofibrosis is characterized by bone marrow angiogenesis and fibrosis, similarly to retinal observations in nAMD. We speculate if we can find lower CXCR3 expression in MPNs, particularly myelofibrosis and if differences are seen between MPNd and MPNn. We also wanted to compare expression in nAMD and intermediate (i)AMD.
Patients in this cross-sectional study were 29 nAMD, 28 iAMD, 35 MPNd, and 27 MPNn. We performed flowcytometry on blood to measure CXCR3 expression.
CD8+CXCR3 expression in nAMD was 6,1%, significantly lower than in iAMD 16%, MPNd 11%, MPNn 12% (p-values<0.05). Similar results were seen for CD4+CXCR3 expression. We also found CXCR3 expression decreasing over the MPN-continuum. For instance, in myelofibrosis, intermediate monocytes expression was 6.2%, significantly lower than 18% in ET and 18% in PV (p-values<0.05).
We find CXCR3 downregulation on T-cells and some monocyte subset in nAMD compared to iAMD, MPNd, and MPNn, in line with previous nAMD studies. We also find CXCR3 downregulation in most monocyte subsets over the MPN continuum. Systemic leukocyte CXCR3 expression could both be involved in changes seen in the retina and the bone marrow. Further understanding the CXCR3-axis in AMD and MPNs may elucidate underlying pathogenic mechanisms and reveal new targets for treatment.
研究发现，患有新生血管性年龄相关性黄斑变性（nAMD）的患者外周血 T 细胞 CXCR3 表达明显低于健康个体。CXCR3 轴具有血管生成和抗纤维化作用。我们最近研究了骨髓增生性肿瘤（MPN）患者的系统性标志物，因为他们 AMD 的患病率更高，并且我们观察到伴有 drusen 的 MPN（MPNd）与正常视网膜的 MPN（MPNn）相比，具有更高的系统性慢性低度炎症和免疫衰老迹象。MPN 从早期癌症阶段（特发性血小板增多症、真性红细胞增多症）发展为晚期骨髓纤维化阶段，呈连续的生物学演变。特别是骨髓纤维化表现为骨髓血管生成和纤维化，与 nAMD 中的视网膜观察结果相似。我们推测是否可以在 MPN 中发现较低的 CXCR3 表达，特别是在骨髓纤维化中，以及在 MPNd 和 MPNn 之间是否存在差异。我们还想比较 nAMD 和中间（i）AMD 之间的表达。
本横断面研究纳入 29 例 nAMD、28 例 iAMD、35 例 MPNd 和 27 例 MPNn。我们对血液进行流式细胞术检测以测量 CXCR3 表达。
nAMD 患者 CD8+CXCR3 表达为 6.1%，明显低于 iAMD 患者的 16%、MPNd 患者的 11%和 MPNn 患者的 12%（p 值<0.05）。CD4+CXCR3 表达也有类似的结果。我们还发现 CXCR3 表达随着 MPN 连续体而降低。例如，在骨髓纤维化中，中间单核细胞的表达为 6.2%，明显低于 ET 的 18%和 PV 的 18%（p 值<0.05）。
与 iAMD、MPNd 和 MPNn 相比，我们在 nAMD 患者中发现 T 细胞和一些单核细胞亚群的 CXCR3 下调，这与之前的 nAMD 研究一致。我们还发现，在 MPN 连续体中，大多数单核细胞亚群的 CXCR3 下调。系统性白细胞 CXCR3 表达可能同时参与视网膜和骨髓的变化。进一步了解 AMD 和 MPN 中的 CXCR3 轴可能阐明潜在的发病机制并揭示新的治疗靶点。
