Volume 46 Issue 11
Nov.  2025
Turn off MathJax
Article Contents
Nan HUO, Junbo ZHAO, Min WANG, Weiqiao AN, Cui CUI. The Relationship between M1/M2 Macrophage Expression and the Severity of Diabetes Retinopathy[J]. Journal of Kunming Medical University, 2025, 46(11): 100-106. doi: 10.12259/j.issn.2095-610X.S20251113
Citation: Nan HUO, Junbo ZHAO, Min WANG, Weiqiao AN, Cui CUI. The Relationship between M1/M2 Macrophage Expression and the Severity of Diabetes Retinopathy[J]. Journal of Kunming Medical University, 2025, 46(11): 100-106. doi: 10.12259/j.issn.2095-610X.S20251113

The Relationship between M1/M2 Macrophage Expression and the Severity of Diabetes Retinopathy

doi: 10.12259/j.issn.2095-610X.S20251113
  • Received Date: 2025-04-16
    Available Online: 2025-12-04
  • Publish Date: 2025-11-25
  •   Objective  To explore the relationship between the M1/M2 macrophages and severity of diabetic retinopathy (DR).   Methods  This retrospective study included 42 patients with or without DR who had type 2 diabetes mellitus (T2DM) and 19 healthy individuals undergoing cataract intraocular surgery without systemic or ocular diseases from Handan Central Hospital between April 2022 and November 2023. Patients with T2DM were divided into three groups: diabetes mellitus with non-dominant diabetic retinopathy (T2DM non-DR group, n = 20), mild and moderate non-proliferative diabetic retinopathy (NPDR)(n = 10) and severe NPDR/ proliferative diabetic retinopathy (PDR)(n = 12). Peripheral blood and aqueous humor were obtained at surgery initiation. The levels of VEGF-A, IL-8, Elafin and TGF-β in the samples were analyzed using kits, and the ratio of M1 macrophages to M2 macrophages was analyzed by flow cytometry.   Results  Among patients with T2DM, there were significant differences in the duration of diabetes, insulin and metformin use among the three groups (P < 0.05). Aqueous humor levels of VEGF-A, IL-8, Elafin, M1 ratio, M2 ratio and TGF-β of each group were significantly different (F = 17.40, 9.492, 4.792, 11.32, 5.768 and 20.38, all P < 0.01). The levels of VEGF-A, IL-8, Elafin, M1 ratio, VD86 and TGF-β in severe NPDR/PDR group were significantly higher than those in healthy control group and T2DM non-DR group (P < 0.05), and the levels of VEGF-A, IL-8 and Elafin in severe NPDR/PDR group were significantly higher than those in mild and moderate NPDR group (P < 0.05). The levels of M1 proportion and TGF-β in aqueous humor of the mild to moderate NPDR group were significantly higher than those in healthy control group and T2DM non-DR group (P < 0.05). The level of M1 in aqueous humor was positively correlated with the levels of M2, Elafin, TGF-β and VEGF-A (r = 0.260, 0.411, 0.726 and 0.304, all P < 0.05), and the level of M2 was positively correlated with the levels of Elafin and TGF-β (r = 0.865, 0.552, all P < 0.01).   Conclusion  The elevation of IL-8 and M1 macrophages in the aqueous humor may promote the occurrence of DR, while the increase of Elafin and M2 macrophages may be a compensatory regulation to chronic inflammation, which is involved in the regulation of local microvascular lesions and fibrosis.
  • loading
  • [1]
    Grauslund J. Diabetic retinopathy screening in the emerging era of artificial intelligence[J]. Diabetologia, 2022, 65(9): 1415-1423. doi: 10.1007/s00125-022-05727-0
    [2]
    Yang X, Huang Z, Xu M, et al. Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy[J]. J Diabetes, 2023, 15(5): 382-396. doi: 10.1111/1753-0407.13373
    [3]
    Fu H, Liu H. Deletion of toll-like receptor 4 ameliorates diabetic retinopathy in mice[J]. Arch Physiol Biochem, 2023, 129(2): 519-525. doi: 10.1080/13813455.2020.1841795
    [4]
    Wang Z, An H, Tang J, et al. Elevated number and density of macrophage-like cell as a novel inflammation biomarker in diabetic macular edema[J]. Sci Rep, 2023, 13(1): 5320. doi: 10.1038/s41598-023-32455-1
    [5]
    Yao Y, Li J, Zhou Y, et al. Macrophage/microglia polarization for the treatment of diabetic retinopathy[J]. Front Endocrinol (Lausanne), 2023, 14: 1276225. doi: 10.3389/fendo.2023.1276225
    [6]
    Hu Q, Zhang X, Peng H, et al. A new modulator of neuroinflammation in diabetic retinopathy: USP25[J]. Inflammation, 2024, 47(4): 1520-1535.
    [7]
    Pan Z, Zhao Y, Zhou S, et al. CD44 drives M1 Drives M1 macrophage polarization in diabetic retinopathy[J]. Curr Eye Res, 2023, 48(8): 770-780. doi: 10.1080/02713683.2023.2210273
    [8]
    Wilkinson C P, Ferris F L 3rd, Klein R E, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales[J]. Ophthalmology, 2003, 110(9): 1677-1682.
    [9]
    American Diabetes Association Professional Practice Committee. 2. classification and diagnosis of diabetes: Standards of medical care in diabetes-2022[J]. Diabetes Care, 2022, 45(suppl 1): S17-S38.
    [10]
    Sun J K, Aiello L P, Abràmoff M D, et al. Updating the staging system for diabetic retinal disease[J]. Ophthalmology, 2021, 128(4): 490-493. doi: 10.1016/j.ophtha.2020.10.008
    [11]
    Tabatabaei-Malazy O, Peimani M, Mohseni S, et al. Therapeutic effects of dietary antioxidative supplements on the management of type 2 diabetes and its complications; umbrella review of observational/trials meta-analysis studies[J]. J Diabetes Metab Disord, 2022, 21(2): 1833-1859. doi: 10.1007/s40200-022-01069-1
    [12]
    Zhang X, Nie Y, Gong Z, et al. Plasma apolipoproteins predicting the occurrence and severity of diabetic retinopathy in patients with type 2 diabetes mellitus[J]. Front Endocrinol (Lausanne), 2022, 13: 915575. doi: 10.3389/fendo.2022.915575
    [13]
    Banete A, Barilo J, Whittaker R, et al. The activated macrophage-a tough fortress for virus invasion: How viruses strike back[J]. Front Microbiol, 2021, 12: 803427. doi: 10.3389/fmicb.2021.803427
    [14]
    Wang J, Lu S, Yang F, et al. The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: A literature review and perspectives[J]. Chin Med, 2021, 16(1): 56. doi: 10.1186/s13020-021-00466-7
    [15]
    Sui A, Chen X, Demetriades A M, et al. Inhibiting NF-κB signaling activation reduces retinal neovascularization by promoting a polarization shift in macrophages[J]. Invest Ophthalmol Vis Sci, 2020, 61(6): 4. doi: 10.1167/iovs.61.6.4
    [16]
    Zhu Y, Zhang L, Lu Q, et al. Identification of different macrophage subpopulations with distinct activities in a mouse model of oxygen-induced retinopathy[J]. Int J Mol Med, 2017, 40(2): 281-292. doi: 10.3892/ijmm.2017.3022
    [17]
    Hu Z, Mao X, Chen M, et al. Single-cell transcriptomics reveals novel role of microglia in fibrovascular membrane of proliferative diabetic retinopathy[J]. Diabetes, 2022, 71(4): 762-773. doi: 10.2337/db21-0551
    [18]
    Burger F, Baptista D, Roth A, et al. Single-cell RNA-seq reveals a crosstalk between hyaluronan receptor LYVE-1-expressing macrophages and vascular smooth muscle cells[J]. Cells, 2022, 11(3): 411. doi: 10.3390/cells11030411
    [19]
    Kheir S, Villeret B, Garcia-Verdugo I, et al. IL-6-elafin genetically modified macrophages as a lung immunotherapeutic strategy against Pseudomonas aeruginosa infections[J]. Mol Ther, 2022, 30(1): 355-369. doi: 10.1016/j.ymthe.2021.08.007
    [20]
    Lodyga M, Hinz B. TGF-β1–A truly transforming growth factor in fibrosis and immunity[J]. Semin Cell Dev Biol, 2020, 101: 123-139. doi: 10.1016/j.semcdb.2019.12.010
    [21]
    Rodriguez R, Lowe K, Keniry M, et al. Involvement of TGF-βsignaling pathway in oxidative stress and diabetic retinopathy[J]. Arch Clin Exp Ophthalmol, 2021, 3(2): 23-28.
    [22]
    Fan J, Shen W, Lee S R, et al. Targeting the notch and TGF-β signaling pathways to prevent retinal fibrosis in vitro and in vivo[J]. Theranostics, 2020, 10(18): 7956-7973. doi: 10.7150/thno.45192
    [23]
    Chen L, Cao Y, Shen Y, et al. Downregulation of PIK3IP1 in retinal microglia promotes retinal pathological neovascularization via PI3K-AKT pathway activation[J]. Sci Rep, 2023, 13(1): 12754. doi: 10.1038/s41598-023-39473-z
  • Relative Articles

    [1] Jiaojiao HAN, Liwei AN, Yangyang XIE, Bin WANG, Jin WANG, Lijun ZHANG. Effects of MiR-126 on Myocardial Remodeling and Macrophage Polarization after Acute Myocardial Infarction. Journal of Kunming Medical University, 2025, 46(11): 43-49.  doi: 10.12259/j.issn.2095-610X.S20251106
    [2] Haixing ZHANG, Jingyun ZHANG, Dandan XU, Lu CAO, Jingjing LI. The Mechanism of miR-23 Regulating PI3K/AKT/mTOR Pathway to Improve Myocardial Angiogenesis in Hypertensive Heart Failure Rats. Journal of Kunming Medical University, 2025, 46(11): 35-42.  doi: 10.12259/j.issn.2095-610X.S20251105
    [3] Ximeng SONG, Shilong YUAN, Zi'ang LU, Maotong XU. Exploring the Molecular Mechanism of Ligustrazine in Spinal Cord Injury Repair Based on Macrophage Autophagy. Journal of Kunming Medical University, 2025, 46(7): 38-45.  doi: 10.12259/j.issn.2095-610X.S20250705
    [4] Haopeng SHENTU, Jing YANG, Weiqing GE, Tao ZHOU, En SONG. The Role of Macrophage Polarization in Thrombotic Diseases. Journal of Kunming Medical University, 2025, 46(1): 1-8.  doi: 10.12259/j.issn.2095-610X.S20250101
    [5] Zhenxiao ZHANG, Jingjing ZHANG, Yun LIAO, Dandan LI, Heng LI, Longding LIU. Effects of HSV-1 Mutant Strain M6 on Macrophage-Mediated Immune Response after Infecting Human Bronchial Epithelial Cells. Journal of Kunming Medical University, 2024, 45(7): 6-13.  doi: 10.12259/j.issn.2095-610X.S20240702
    [6] Liang ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Yang KE, Wei ZHANG. M2 Macrophage-derived Exosome miR-1246 Regulates the Growth and Invasion of Gastric Cancer Cells. Journal of Kunming Medical University, 2023, 44(7): 69-77.  doi: 10.12259/j.issn.2095-610X.S20230724
    [7] Weijia ZHAO, Hongbin LI, Zonghan CHEN. Effects of Micafungin on the Activity of Candida Smooth in Macrophages. Journal of Kunming Medical University, 2022, 43(1): 14-19.  doi: 10.12259/j.issn.2095-610X.S20220142
    [8] Yu-xing XIONG, Jun TANG, Ru-yun LIN, Jia-min NIE, Min-jie ZHOU, Ju-wei SHAO. Correlation between Cerebral Perfusion and Retinal Oxygenation Response of Diabetic Retinopathy in Type 2 Diabetes Mellitus. Journal of Kunming Medical University, 2021, 42(10): 76-83.  doi: 10.12259/j.issn.2095-610X.S20211046
    [9] Wang Jin Rui , Yang Ying . . Journal of Kunming Medical University, 2019, 40(04): 131-135.
    [10] Zhang Xiao Chao , Shen Zhi Qiang , Yang Ren Hua , Tang Chuan Jing , Bai Lin Ying , He Bo , Chen Peng , Yao Rong Cheng . Effects of Corilagin on Expression of CRP in OX-LDL Injured Macrophage Cells. Journal of Kunming Medical University, 2017, 38(08): 1-5.
    [11] Yang Rong , Yang Ying . . Journal of Kunming Medical University, 2017, 38(05): 44-49.
    [12] Lei Huo . The Current Situation of the Prevention and Treatment of Diabetic Eye Disease in Yunnan Province. Journal of Kunming Medical University,
    [13] Xie Yuan Run . Experimental Study on The Chemotaxis of Blood Monocyte to Three Kinds of Glioma Cell Lines(U87,U251 and T98G) in Vitro. Journal of Kunming Medical University,
    [14] Bian Hai Xia . . Journal of Kunming Medical University,
    [15] Liu Dong . . Journal of Kunming Medical University,
    [16] Yang Jing . . Journal of Kunming Medical University,
    [17] Zhu Zhao . . Journal of Kunming Medical University,
    [18] Shi Zhao Kun . . Journal of Kunming Medical University,
    [19] Cha Xue Ping . . Journal of Kunming Medical University,
    [20] . The Relationship between Glycated Hemoglobin and Diabetic Retinopathy. Journal of Kunming Medical University,
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)  / Tables(2)

    Article Metrics

    Article views (48) PDF downloads(1) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return