Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2022 May 27;13:841813. doi: 10.3389/fendo.2022.841813. eCollection 2022.
Diabetic retinopathy (DR), especially proliferative diabetic retinopathy (PDR), is the major cause of irreversible blindness in the working-age population. Increasing evidence indicates that immune cells and the inflammatory microenvironment play an important role during PDR development. Herein, we aim to explore the immune landscape of PDR and then identify potential biomarkers correlated with specific infiltrating immune cells.
We mined and re-analyzed PDR-related datasets from the Gene Expression Omnibus (GEO) database. Using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm, we investigated the infiltration of 22 types of immune cells in all selected samples; analyses of differences and correlations between infiltrating cells were used to reveal the immune landscape of PDR. Thereafter, weighted gene co-expression network analysis (WGCNA) and differential expression analysis were applied to identify the hub genes on M2 macrophages that may affect PDR progression.
Significant differences were found between infiltration levels of immune cells in fibrovascular membranes (FVMs) from PDR and normal retinas. The percentages of follicular helper T cells, M1 macrophages, and M2 macrophages were increased significantly in FVMs. Integrative analysis combining the differential expression and co-expression revealed the M2 macrophage-related hub genes in PDR. Among these, , and showed increased expression in FVM and may be potential biomarkers for PDR.
Our findings provide novel insights into the immune mechanisms involved in PDR. , and are M2 macrophage-related biomarkers, further study of these genes could inform novel ideas and basis for the understanding of disease progression and targeted treatment of PDR.
糖尿病视网膜病变（DR），尤其是增生性糖尿病视网膜病变（PDR），是工作年龄人群中不可逆失明的主要原因。越来越多的证据表明，免疫细胞和炎症微环境在 PDR 发展过程中起着重要作用。在此，我们旨在探索 PDR 的免疫景观，然后确定与特定浸润免疫细胞相关的潜在生物标志物。
我们从基因表达综合数据库（GEO）中挖掘和重新分析了与 PDR 相关的数据集。使用估计相对 RNA 转录物亚群的细胞类型识别（CIBERSORT）算法，我们研究了所有选定样本中 22 种免疫细胞的浸润情况；分析浸润细胞之间的差异和相关性，以揭示 PDR 的免疫景观。然后，应用加权基因共表达网络分析（WGCNA）和差异表达分析，鉴定影响 PDR 进展的 M2 巨噬细胞上的枢纽基因。
在 PDR 和正常视网膜的血管纤维膜（FVM）中，免疫细胞浸润水平存在显著差异。滤泡辅助 T 细胞、M1 巨噬细胞和 M2 巨噬细胞的比例在 FVM 中显著增加。将差异表达和共表达相结合的综合分析揭示了 PDR 中与 M2 巨噬细胞相关的枢纽基因。其中，和在 FVM 中表达增加，可能是 PDR 的潜在生物标志物。
我们的研究结果为 PDR 涉及的免疫机制提供了新的见解。和是 M2 巨噬细胞相关的生物标志物，进一步研究这些基因可能为理解疾病进展和 PDR 的靶向治疗提供新的思路和依据。
