Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2025 Volume 56 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2025 Volume 56 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Mechanisms of action of retinal microglia in diabetic retinopathy (Review)

  • Authors:
    • Yuyang Bai
    • Xinrong Wang
    • Fan Qi
    • Xiaoyang Zuo
    • Gang Zou
  • View Affiliations / Copyright

    Affiliations: Third Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China, Department of Ophthalmology, Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Third Clinical School of Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
    Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 202
    |
    Published online on: September 22, 2025
       https://doi.org/10.3892/ijmm.2025.5643
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Diabetic retinopathy (DR), a leading cause of blindness in diabetic microvascular complications, is pathologically associated with the dynamic regulation of retinal microglia. The present review systematically elucidated the dual roles of microglia in DR pathogenesis. Under physiological conditions, microglia maintain blood‑retinal barrier (BRB) integrity by phagocytosing metabolic debris and secreting neurotrophic factors. However, hyperglycaemic stress induces pathological M1 polarization, triggering a cytokine storm (TNF‑α and IL‑1β) via the Toll‑like receptor 4/myeloid differentiation primary response 88/NF‑κB signalling axis, which synergizes with proangiogenic factors (such as VEGF and insulin‑like growth factor 1) to exacerbate BRB breakdown and pathological neovascularization. Notably, activated microglia amplify inflammatory cascades through astrocyte‑Müller cell interaction networks, accelerating neurovascular unit dysfunction. Emerging therapeutic strategies targeting microglial polarization homeostasis (such as promoting M2 anti‑inflammatory phenotypic shifts) and blocking critical inflammatory signalling pathways present novel opportunities for developing multitarget therapeutic agents with combined neuroprotective and anti‑vasopermeability properties. By elucidating microglial heterogeneity and intercellular regulatory networks, the present review highlighted the importance of precise modulation of immune homeostasis in DR management, providing a theoretical foundation for overcoming the limitations of single‑target therapies.
View Figures

Figure 1

Mechanisms of vascular and neuronal
modulation of retinal microglia in DR. Under physiological
conditions, M2 polarization dominates, releasing anti-inflammatory
and neurotrophic factors such as IL-4, IL-10, TGF-β and BDNF.
Microglia maintain retinal homeostasis via phagocytosis of
metabolic waste, cell migration and interactions with Müller and
astrocytes, preserving the BRB. In pathological states, M1
polarization prevails, producing pro-inflammatory and angiogenic
factors, including IL-1β, IL-6, TNF-α, VEGF-A and IGF-1. These
factors disrupt the BRB, causing BRB leakage and RNV. The imbalance
between M1 and M2 polarization also disrupts cellular interactions,
retinal homeostasis and the neurovascular-immune network,
ultimately damaging the NVU. DR, diabetic retinopathy; BDNF,
brain-derived neurotrophic factor; BRB, blood-retinal barrier; RNV,
retinal neovascularization; IGF-1, insulin-like growth factor 1;
NVU, neurovascular unit.

Figure 2

Composition of neurovascular unit.
The neurovascular unit comprises endothelial cells, pericytes,
basement membrane, tight junctions, microglia, Müller cells and
ganglion cells, which together maintain retinal homeostasis.
Endothelial cells line blood vessels and form tight junctions
regulating substance exchange. Pericytes embedded in the basement
membrane support vascular stability. Microglia serve as resident
immune cells, while Müller cells provide metabolic and structural
support to neurons. Ganglion cells transmit visual information.
Collectively, these components regulate the blood-retinal barrier,
blood flow and support neuronal function.

Figure 3

Effects of hyperglycaemic
microenvironment on the activation of microglia. Diabetes leads to
elevated blood glucose levels, which activate several metabolic
pathways: the polyol pathway, hexosamine pathway, PKC-β/δ pathway,
AGE accumulation and ANG-II signalling. These pathways converge to
activate NF-κB and increase ROS production. The interplay between
NF-κB and ROS creates a positive feedback loop, further amplifying
the inflammatory response. This results in the release of
pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β,
ultimately promoting M1 polarization of immune cells and impairing
M2 polarization. AGE, advanced glycation end products; ANG-II,
angiotensin II; ROS, reactive oxygen species.

Figure 4

Signalling pathways and cellular
interactions mediated by microglia in DR. In DR, microglia express
receptors such as C3a and C5a receptors, VEGFR and TLR4. The
activation of these receptors triggers intracellular signalling
pathways which subsequently activate downstream kinases. These
signalling cascades lead to the activation of transcription factors
such as NF-κB, resulting in the production and release of
pro-inflammatory cytokines including IL-1β, TNF-α and IL-6. The
released pro-inflammatory cytokines then act on Müller cells,
promoting the release of VEGF. This process highlights the role of
microglia in mediating inflammatory responses and angiogenesis in
DR through these signalling pathways. DR, diabetic retinopathy;
TLR-4, Toll-like receptor 4; MyD88, myeloid differentiation primary
response 88; IRAK-4, interleukin-1 receptor-associated kinase 4;
TRAF6, TNF receptor-associated factor 6; IKK, IκB kinase.
View References

1 

World Health Organization (WHO): Global report on diabetes. WHO; Geneva: pp. 1–88. 2016

2 

Altmann C and Schmidt MHH: The role of microglia in diabetic retinopathy: Inflammation, microvasculature defects and neurodegeneration. Int J Mol Sci. 19:1102018. View Article : Google Scholar : PubMed/NCBI

3 

Obrosova IG and Kador PF: Aldose reductase/polyol inhibitors for diabetic retinopathy. Curr Pharm Biotechnol. 12:373–385. 2011. View Article : Google Scholar

4 

Cheung N, Mitchell P and Wong TY: Diabetic retinopathy. Lancet. 376:124–136. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, Bikbov MM, Wang YX, Tang Y, Lu Y, et al: Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis. Ophthalmology. 128:1580–1591. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Yang QH, Zhang Y, Zhang XM and Li XR: Prevalence of diabetic retinopathy, proliferative diabetic retinopathy and non-proliferative diabetic retinopathy in Asian T2DM patients: A systematic review and meta-analysis. Int J Ophthalmol. 12:302–311. 2019.PubMed/NCBI

7 

Cheyne CP, Burgess PI, Broadbent DM, García-Fiñana M, Stratton IM, Criddle T, Wang A, Alshukri A, Rahni MM, Vazquez-Arango P, et al: Incidence of sight-threatening diabetic retinopathy in an established urban screening programme: An 11-year cohort study. Diabet Med. 38:e145832021. View Article : Google Scholar : PubMed/NCBI

8 

Das A, Stroud S, Mehta A and Rangasamy S: New treatments for diabetic retinopathy. Diabetes Obes Metab. 17:219–230. 2015. View Article : Google Scholar

9 

Wei L, Sun X, Fan C, Li R, Zhou S and Yu H: The pathophysiological mechanisms underlying diabetic retinopathy. Front Cell Dev Biol. 10:9636152022. View Article : Google Scholar : PubMed/NCBI

10 

Arroba AI, Alcalde-Estevez E, García-Ramírez M, Cazzoni D, de la Villa P, Sánchez-Fernández EM, Mellet CO, García Fernández JM, Hernández C, Simó R and Valverde ÁM: Modulation of microglia polarization dynamics during diabetic retinopathy in db/db mice. Biochim Biophys Acta. 1862:1663–1674. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Kinuthia UM, Wolf A and Langmann T: Microglia and inflammatory responses in diabetic retinopathy. Front Immunol. 11:5640772020. View Article : Google Scholar : PubMed/NCBI

12 

Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK and Ting JPY: TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 4:1116–1122. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Prinz M, Jung S and Priller J: Microglia biology: One century of evolving concepts. Cell. 179:292–311. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Yang S, Zhang J and Chen L: The cells involved in the pathological process of diabetic retinopathy. Biomed Pharmacother. 132:1108182020. View Article : Google Scholar : PubMed/NCBI

15 

Van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG and Langevoort HL: The mononuclear phagocyte system: A new classification of macrophages, monocytes, and their precursor cells. Bull World Health Organ. 46:845–852. 1972.PubMed/NCBI

16 

Rao B, Liu X, Xiao J, Wu X, He F, Yang Q, Zhao W, Lin X and Zhang J: Microglia heterogeneity during neuroinflammation and neurodegeneration in the mouse retina. Brain Struct Funct. 230:192024. View Article : Google Scholar : PubMed/NCBI

17 

Karlstetter M, Scholz R, Rutar M, Wong WT, Provis JM and Langmann T: Retinal microglia: Just bystander or target for therapy? Prog Retin Eye Res. 45:30–57. 2015. View Article : Google Scholar

18 

Usui Y: Elucidation of pathophysiology and novel treatment for diabetic macular edema derived from the concept of neurovascular unit. JMA J. 3:201–207. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Hughes S, Yang H and Chan-Ling T: Vascularization of the human fetal retina: Roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci. 41:1217–1228. 2000.

20 

Frost JL and Schafer DP: Microglia: Architects of the developing nervous system. Trends Cell Biol. 26:587–597. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Rymo SF, Gerhardt H, Wolfhagen Sand F, Lang R, Uv A and Betsholtz C: A two-way communication between microglial cells and angiogenic sprouts regulates angiogenesis in aortic ring cultures. PLoS One. 6:e158462011. View Article : Google Scholar : PubMed/NCBI

22 

Haupt F, Krishnasamy K, Napp LC, Augustynik M, Limbourg A, Gamrekelashvili J, Bauersachs J, Haller H and Limbourg FP: Retinal myeloid cells regulate tip cell selection and vascular branching morphogenesis via Notch ligand Delta-like 1. Sci Rep. 9:97982019. View Article : Google Scholar : PubMed/NCBI

23 

Endo Y, Asanuma D, Namiki S, Sugihara K, Hirose K, Uemura A, Kubota Y and Miura T: Quantitative modeling of regular retinal microglia distribution. Sci Rep. 11:226712021. View Article : Google Scholar : PubMed/NCBI

24 

Asare-Bediako B, Adu-Agyeiwaah Y, Abad A, Li Calzi S, Floyd JL, Prasad R, DuPont M, Asare-Bediako R, Bustelo XR and Grant MB: Hematopoietic cells influence vascular development in the retina. Cells. 11:32072022. View Article : Google Scholar : PubMed/NCBI

25 

Perochon T, Krsnik Z, Massimo M, Ruchiy Y, Romero AL, Mohammadi E, Li X, Long KR, Parkkinen L, Blomgren K, et al: Unraveling microglial spatial organization in the developing human brain with DeepCellMap, a deep learning approach coupled with spatial statistics. Nat Commun. 16:15772025. View Article : Google Scholar : PubMed/NCBI

26 

Li F, Jiang D and Samuel MA: Microglia in the developing retina. Neural Dev. 14:122019. View Article : Google Scholar

27 

Zhou LY, Liu ZG, Sun YQ, Li YZ, Teng ZQ and Liu CM: Preserving blood-retinal barrier integrity: A path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy. Cell Regen. 14:132025. View Article : Google Scholar : PubMed/NCBI

28 

Klaassen I, Van Noorden CJF and Schlingemann RO: Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res. 34:19–48. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Guymer RH, Bird AC and Hageman GS: Cytoarchitecture of choroidal capillary endothelial cells. Invest Ophthalmol Vis Sci. 45:1660–1666. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Hormel TT, Jia Y, Jian Y, Hwang TS, Bailey ST, Pennesi ME, Wilson DJ, Morrison JC and Huang D: Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography. Prog Retin Eye Res. 80:1008782021. View Article : Google Scholar :

31 

Amoaku WM, Ghanchi F, Bailey C, Banerjee S, Banerjee S, Downey L, Gale R, Hamilton R, Khunti K, Posner E, et al: Diabetic retinopathy and diabetic macular oedema pathways and management: UK consensus working group. Eye (Lond). 34(Suppl 1): S1–S51. 2020. View Article : Google Scholar

32 

Opdenakker G and Abu El-Asrar A: Metalloproteinases mediate diabetes-induced retinal neuropathy and vasculopathy. Cell Mol Life Sci. 76:3157–3166. 2019. View Article : Google Scholar : PubMed/NCBI

33 

O'Leary F and Campbell M: The blood-retina barrier in health and disease. FEBS J. 290:878–891. 2023. View Article : Google Scholar

34 

Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA and Stevens B: Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 74:691–705. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Zhu X, Hong J and Zhou X: Biological immune mechanism of retina. Front Biosci (Landmark Ed). 28:3632023. View Article : Google Scholar

36 

Kumar A, Kumar A, Kumar J, Bai G, Jeewnani R, Dembra M, Kanwal K, Qadeer U, Khawar MH, Yaseen Khan I, et al: Comparative efficacy of anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids in managing diabetic retinopathy-associated diabetic macular edema: A meta-analysis and comprehensive systematic review. Cureus. 16:e519102024.PubMed/NCBI

37 

Lee WJ, Kang MH, Seong M and Cho HY: Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion. Br J Ophthalmol. 96:1426–1430. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Meng C, Gu C, He S, Su T, Lhamo T, Draga D and Qiu Q: Pyroptosis in the retinal neurovascular unit: New insights into diabetic retinopathy. Front Immunol. 12:7630922021. View Article : Google Scholar : PubMed/NCBI

39 

Romero-Aroca P, Baget-Bernaldiz M, Pareja-Rios A, Lopez-Galvez M, Navarro-Gil R and Verges R: Diabetic macular edema pathophysiology: Vasogenic versus inflammatory. J Diabetes Res. 2016:21562732016. View Article : Google Scholar : PubMed/NCBI

40 

Zhang Y, Zhao L, Wang X, Ma W, Lazere A, Qian HH, Zhang J, Abu-Asab M, Fariss RN, Roger JE and Wong WT: Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation. Sci Adv. 4:eaap84922018. View Article : Google Scholar : PubMed/NCBI

41 

Zhao L, Zabel MK, Wang X, Ma W, Shah P, Fariss RN, Qian H, Parkhurst CN, Gan WB and Wong WT: Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO Mol Med. 7:1179–1197. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Wang J, He W and Zhang J: A richer and more diverse future for microglia phenotypes. Heliyon. 9:e147132023. View Article : Google Scholar : PubMed/NCBI

43 

Fouda AY, Xu Z, Suwanpradid J, Rojas M, Shosha E, Lemtalsi T, Patel C, Xing J, Zaidi SA, Zhi W, et al: Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair. Cell Death Dis. 13:7452022. View Article : Google Scholar : PubMed/NCBI

44 

Li X, Yu ZW, Li HY, Yuan Y, Gao XY and Kuang HY: Retinal microglia polarization in diabetic retinopathy. Vis Neurosci. 38:E0062021. View Article : Google Scholar : PubMed/NCBI

45 

Ikeda T, Nakamura K, Kida T and Oku H: Possible roles of anti-type II collagen antibody and innate immunity in the development and progression of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 260:387–403. 2022. View Article : Google Scholar :

46 

Ibrahim AS, El-Shishtawy MM, Peña A Jr and Liou GI: Genistein attenuates retinal inflammation associated with diabetes by targeting of microglial activation. Mol Vis. 16:2033–2042. 2010.PubMed/NCBI

47 

Cukras CA, Petrou P, Chew EY, Meyerle CB and Wong WT: Oral minocycline for the treatment of diabetic macular edema (DME): Results of a phase I/II clinical study. Invest Ophthalmol Vis Sci. 53:3865–3874. 2012. View Article : Google Scholar : PubMed/NCBI

48 

Madeira MH, Boia R, Santos PF, Ambrósio AF and Santiago AR: Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases. Mediators Inflamm. 2015:6730902015. View Article : Google Scholar : PubMed/NCBI

49 

Grigsby JG, Cardona SM, Pouw CE, Muniz A, Mendiola AS, Tsin ATC, Allen DM and Cardona AE: The role of microglia in diabetic retinopathy. J Ophthalmol. 2014:7057832014. View Article : Google Scholar : PubMed/NCBI

50 

Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, Amit I, Audinat E, Bechmann I, Bennett M, et al: Microglia states and nomenclature: A field at its crossroads. Neuron. 110:3458–3483. 2022. View Article : Google Scholar : PubMed/NCBI

51 

Sun N, Victor MB, Park YP, Xiong X, Scannail AN, Leary N, Prosper S, Viswanathan S, Luna X, Boix CA, et al: Human microglial state dynamics in Alzheimer's disease progression. Cell. 186:4386–4403.e29. 2023. View Article : Google Scholar : PubMed/NCBI

52 

He J, Fu Y, Ge L, Dai J, Fang Y, Li Y, Gu X, Tao Z, Zou T, Li M, et al: Disease-associated microglial activation prevents photoreceptor degeneration by suppressing the accumulation of cell debris and neutrophils in degenerating rat retinas. Theranostics. 12:2687–2706. 2022. View Article : Google Scholar : PubMed/NCBI

53 

Shemer A, Grozovski J, Tay TL, Tao J, Volaski A, Süß P, Ardura-Fabregat A, Gross-Vered M, Kim JS, David E, et al: Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. Nat Commun. 9:52062018. View Article : Google Scholar : PubMed/NCBI

54 

Buttgereit A, Lelios I, Yu X, Vrohlings M, Krakoski NR, Gautier EL, Nishinakamura R, Becher B and Greter M: Sall1 is a transcriptional regulator defining microglia identity and function. Nat Immunol. 17:1397–1406. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Jurga AM, Paleczna M and Kuter KZ: Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci. 14:1982020. View Article : Google Scholar : PubMed/NCBI

56 

Wolf J, Boneva S, Rosmus DD, Agostini H, Schlunck G, Wieghofer P, Schlecht A and Lange C: In-depth molecular profiling specifies human retinal microglia identity. Front Immunol. 13:8631582022. View Article : Google Scholar : PubMed/NCBI

57 

Masuda T, Amann L, Sankowski R, Staszewski O, Lenz M, D'Errico P, Snaidero N, Costa Jordão MJ, Böttcher C, Kierdorf K, et al: Novel Hexb-based tools for studying microglia in the CNS. Nat Immunol. 21:802–815. 2020. View Article : Google Scholar : PubMed/NCBI

58 

Kenkhuis B, Somarakis A, Kleindouwel LRT, Van Roon-Mom WMC, Höllt T and Van Der Weerd L: Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease. Neurobiol Dis. 167:1056842022. View Article : Google Scholar : PubMed/NCBI

59 

Qin Z, He S, Yang C, Yung JSY, Chen C, Leung CKS, Liu K and Qu JY: Adaptive optics two-photon microscopy enables near-diffraction-limited and functional retinal imaging in vivo. Light Sci Appl. 9:792020. View Article : Google Scholar : PubMed/NCBI

60 

Wu MY, Yiang GT, Lai TT and Li CJ: The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxidative Med Cell Longev. 2018:34201872018. View Article : Google Scholar

61 

Lv K, Ying H, Hu G, Hu J, Jian Q and Zhang F: Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy. Front Immunol. 13:9427682022. View Article : Google Scholar : PubMed/NCBI

62 

Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J and Brownlee M: Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA. 97:12222–12226. 2000. View Article : Google Scholar : PubMed/NCBI

63 

Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C and Brownlee M: Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Investig. 112:1049–1057. 2003. View Article : Google Scholar : PubMed/NCBI

64 

Kowluru RA: Effect of advanced glycation end products on accelerated apoptosis of retinal capillary cells under in vitro conditions. Life Sci. 76:1051–1060. 2005. View Article : Google Scholar

65 

Glomb MA and Monnier VM: Mechanism of protein modification by glyoxal and glycolaldehyde, reactive intermediates of the maillard reaction. J Biol Chem. 270:10017–10026. 1995. View Article : Google Scholar : PubMed/NCBI

66 

Funatsu H and Yamashita H: Pathogenesis of diabetic retinopathy and the renin-angiotensin system. Ophthalmic Physiol Opt. 23:495–501. 2003. View Article : Google Scholar : PubMed/NCBI

67 

Cai Y, Li W, Tu H, Chen N, Zhong Z, Yan P and Dong J: Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κB signaling. Bioorg Med Chem Lett. 27:1835–1839. 2017. View Article : Google Scholar : PubMed/NCBI

68 

Stitt AW: The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp Mol Pathol. 75:95–108. 2003. View Article : Google Scholar : PubMed/NCBI

69 

Yamagishi SI and Matsui T: Advanced glycation end products (AGEs), oxidative stress and diabetic retinopathy. Curr Pharm Biotechnol. 12:362–368. 2011. View Article : Google Scholar

70 

Song J and Lee JE: ASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition. Front Cell Neurosci. 9:1982015. View Article : Google Scholar : PubMed/NCBI

71 

Du A, Xie Y, Ouyang H, Lu B, Jia W, Xu H and Ji L: Si-miao-yong-an decoction for diabetic retinopathy: A combined network pharmacological and in vivo approach. Front Pharmacol. 12:7631632021. View Article : Google Scholar : PubMed/NCBI

72 

Vargas-Soria M, García-Alloza M and Corraliza-Gómez M: Effects of diabetes on microglial physiology: A systematic review of in vitro, preclinical and clinical studies. J Neuroinflammation. 20:572023. View Article : Google Scholar : PubMed/NCBI

73 

Quiriconi P, Hristov V, Aburaya M, Greferath U, Jobling AI and Fletcher EL: The role of microglia in the development of diabetic retinopathy. NPJ Metab Health Dis. 2:72024. View Article : Google Scholar : PubMed/NCBI

74 

Cai L, Xia M and Zhang F: Redox regulation of immunometabolism in microglia underpinning diabetic retinopathy. Antioxidants (Basel). 13:4232024. View Article : Google Scholar : PubMed/NCBI

75 

Yamaguchi M, Nakao S, Arima M, Little K, Singh A, Wada I, Kaizu Y, Zandi S, Garweg JG, Matoba T, et al: Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation. Diabetologia. 67:2329–2345. 2024. View Article : Google Scholar : PubMed/NCBI

76 

Wang J, Liu X, Wei W, Yang J, Li Q, Chu S, Liu P, Zhang J and He W: Regulation of oxygen-glucose deprivation/reperfusion-induced inflammatory responses and M1-M2 phenotype switch of BV2 microglia by lobetyolin. Metab Brain Dis. 38:2627–2644. 2023. View Article : Google Scholar : PubMed/NCBI

77 

Nian S, Lo ACY, Mi Y, Ren K and Yang D: Neurovascular unit in diabetic retinopathy: Pathophysiological roles and potential therapeutical targets. Eye Vis (Lond Engl). 8:152021. View Article : Google Scholar

78 

Inada M, Xu H, Takeuchi M, Ito M and Chen M: Microglia increase tight-junction permeability in coordination with Müller cells under hypoxic condition in an in vitro model of inner blood-retinal barrier. Exp Eye Res. 205:1084902021. View Article : Google Scholar

79 

Fang M, Wan W, Li Q, Wan W, Long Y, Liu H and Yang X: Asiatic acid attenuates diabetic retinopathy through TLR4/MyD88/NF-κB p65 mediated modulation of microglia polarization. Life Sci. 277:1195672021. View Article : Google Scholar

80 

Mehrabadi AR, Korolainen MA, Odero G, Miller DW and Kauppinen TM: Poly(ADP-ribose) polymerase-1 regulates microglia mediated decrease of endothelial tight junction integrity. Neurochem Int. 108:266–271. 2017. View Article : Google Scholar : PubMed/NCBI

81 

Usui-Ouchi A, Usui Y, Kurihara T, Aguilar E, Dorrell MI, Ideguchi Y, Sakimoto S, Bravo S and Friedlander M: Retinal microglia are critical for subretinal neovascular formation. JCI Insight. 5:e1373172020. View Article : Google Scholar : PubMed/NCBI

82 

Xie H, Zhang C, Liu D, Yang Q, Tang L, Wang T, Tian H, Lu L, Xu JY, Gao F, et al: Erythropoietin protects the inner blood-retinal barrier by inhibiting microglia phagocytosis via Src/Akt/cofilin signalling in experimental diabetic retinopathy. Diabetologia. 64:211–225. 2021. View Article : Google Scholar

83 

Zhang T, Ouyang H, Mei X, Lu B, Yu Z, Chen K, Wang Z and Ji L: Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells via inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway. FASEB J. 33:11776–11790. 2019. View Article : Google Scholar : PubMed/NCBI

84 

Behnke V, Wolf A and Langmann T: The role of lymphocytes and phagocytes in age-related macular degeneration (AMD). Cell Mol Life Sci. 77:781–788. 2020. View Article : Google Scholar : PubMed/NCBI

85 

Ogura S, Baldeosingh R, Bhutto IA, Kambhampati SP, McLeod DS, Edwards MM, Rais R, Schubert W and Lutty GA: A role for mast cells in geographic atrophy. FASEB J. 34:10117–10131. 2020. View Article : Google Scholar : PubMed/NCBI

86 

Lueck K, Busch M, Moss SE, Greenwood J, Kasper M, Lommatzsch A, Pauleikhoff D and Wasmuth S: Complement stimulates retinal pigment epithelial cells to undergo pro-inflammatory changes. Ophthalmic Res. 54:195–203. 2015. View Article : Google Scholar : PubMed/NCBI

87 

Fu X, Feng S, Qin H, Yan L, Zheng C and Yao K: Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy. Front Mol Neurosci. 16:11002542023. View Article : Google Scholar : PubMed/NCBI

88 

Ding X, Gu R, Zhang M, Ren H, Shu Q, Xu G and Wu H: Microglia enhanced the angiogenesis, migration and proliferation of co-cultured RMECs. BMC Ophthalmol. 18:2492018. View Article : Google Scholar : PubMed/NCBI

89 

Hu A, Schmidt MHH and Heinig N: Microglia in retinal angiogenesis and diabetic retinopathy. Angiogenesis. 27:311–331. 2024. View Article : Google Scholar : PubMed/NCBI

90 

Tang L, Xu GT and Zhang JF: Inflammation in diabetic retinopathy: Possible roles in pathogenesis and potential implications for therapy. Neural Regen Res. 18:976–982. 2023. View Article : Google Scholar :

91 

Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, et al: Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown. JCI Insight. 2:e909052017. View Article : Google Scholar : PubMed/NCBI

92 

He C, Liu Y, Huang Z, Yang Z, Zhou T, Liu S, Hao Z, Wang J, Feng Q, Liu Y, et al: A specific RIP3+ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism. Proc Natl Acad Sci USA. 118:e20232901182021. View Article : Google Scholar

93 

Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, et al: Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 13:868–873. 2007. View Article : Google Scholar : PubMed/NCBI

94 

Yin J, Xu WQ, Ye MX, Zhang Y, Wang HY, Zhang J, Li Y and Wang YS: Up-regulated basigin-2 in microglia induced by hypoxia promotes retinal angiogenesis. J Cell Mol Med. 21:3467–3480. 2017. View Article : Google Scholar : PubMed/NCBI

95 

Zhao C, Liu Y, Meng J, Wang X, Liu X, Li W, Zhou Q, Xiang J, Li N and Hou S: LGALS3BP in microglia promotes retinal angiogenesis through PI3K/AKT pathway during hypoxia. Invest Ophthalmol Vis Sci. 63:252022. View Article : Google Scholar : PubMed/NCBI

96 

Murinello S, Usui Y, Sakimoto S, Kitano M, Aguilar E, Friedlander HM, Schricker A, Wittgrove C, Wakabayashi Y, Dorrell MI, et al: miR-30a-5p inhibition promotes interaction of Fas+ endothelial cells and FasL+ microglia to decrease pathological neovascularization and promote physiological angiogenesis. Glia. 67:332–344. 2019. View Article : Google Scholar

97 

Luo Q, Jiang Z, Jiang J, Wan L, Li Y, Huang Y, Qiu J, Yu K and Zhuang J: Tsp-1+ microglia attenuate retinal neovascularization by maintaining the expression of Smad3 in endothelial cells through exosomes with decreased miR-27a-5p. Theranostics. 13:3689–3706. 2023. View Article : Google Scholar :

98 

Hu Y, Wei T, Gao S and Cheng Q: Anti-angiogenic and anti-inflammatory effects of CD200-CD200R1 axis in oxygen-induced retinopathy mice model. Inflamm Res. 68:945–955. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Dejda A, Mawambo G, Daudelin JF, Miloudi K, Akla N, Patel C, Andriessen EMMA, Labrecque N, Sennlaub F and Sapieha P: Neuropilin-1-expressing microglia are associated with nascent retinal vasculature yet dispensable for developmental angiogenesis. Invest Ophthalmol Vis Sci. 57:1530–1536. 2016. View Article : Google Scholar : PubMed/NCBI

100 

Dejda A, Mawambo G, Cerani A, Miloudi K, Shao Z, Daudelin JF, Boulet S, Oubaha M, Beaudoin F, Akla N, et al: Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk. J Clin Investig. 124:4807–4822. 2014. View Article : Google Scholar : PubMed/NCBI

101 

Bai Q, Wang X, Yan H, Wen L, Zhou Z, Ye Y, Jing Y, Niu Y, Wang L, Zhang Z, et al: Microglia-derived Spp1 promotes pathological retinal neovascularization via activating endothelial Kit/Akt/mTOR signaling. J Pers Med. 13:1462023. View Article : Google Scholar : PubMed/NCBI

102 

Zhou ZY, Chang TF, Lin ZB, Jing YT, Wen LS, Niu YL, Bai Q, Guo CM, Sun JX, Wang YS and Dou GR: Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via notch inhibition by competitively binding to Jag1. Cell Death Dis. 14:3802023. View Article : Google Scholar : PubMed/NCBI

103 

Li L, Sun B, Harris OA and Luo J: TGF-β signaling in microglia: A key regulator of development, homeostasis and reactivity. Biomedicines. 12:24682024. View Article : Google Scholar

104 

Wiens KR, Wasti N, Ulloa OO and Klegeris A: Diversity of microglia-derived molecules with neurotrophic properties that support neurons in the central nervous system and other tissues. Molecules. 29:55252024. View Article : Google Scholar : PubMed/NCBI

105 

Liu W, Tong B, Xiong J, Zhu Y, Lu H, Xu H, Yang X, Wang F, Yu P and Hu Y: Identification of macrophage polarisation and mitochondria-related biomarkers in diabetic retinopathy. J Transl Med. 23:232025. View Article : Google Scholar : PubMed/NCBI

106 

Amankwa CE, Acha LG, Dibas A, Chavala SH, Roth S, Mathew B and Acharya S: Neuroprotective and anti-inflammatory activities of hybrid small-molecule SA-10 in ischemia/reperfusion-induced retinal neuronal injury models. Cells. 13:3962024. View Article : Google Scholar : PubMed/NCBI

107 

Paisley CE and Kay JN: Seeing stars: Development and function of retinal astrocytes. Dev Biol. 478:144–154. 2021. View Article : Google Scholar : PubMed/NCBI

108 

Chan-Ling T: Development of the retinal vasculature. Encyclopedia of the eye. D'Amore P: Academic Press; Cambridge: pp. 22–33. 2010, View Article : Google Scholar

109 

Gnanaguru G, Tabor SJ, Bonilla GM, Sadreyev R, Yuda K, Köhl J and Connor KM: Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis. Development. 150:dev2010472023. View Article : Google Scholar : PubMed/NCBI

110 

Checchin D, Sennlaub F, Levavasseur E, Leduc M and Chemtob S: Potential role of microglia in retinal blood vessel formation. Invest Ophthalmol Vis Sci. 47:3595–3602. 2006. View Article : Google Scholar : PubMed/NCBI

111 

Wang M, Ma W, Zhao L, Fariss RN and Wong WT: Adaptive Müller cell responses to microglial activation mediate neuroprotection and coordinate inflammation in the retina. J Neuroinflammation. 8:1732011. View Article : Google Scholar

112 

Tewari M, Michalski S and Egan TM: Modulation of microglial function by ATP-gated P2X7 receptors: Studies in rat, mice and human. Cells. 13:1612024. View Article : Google Scholar : PubMed/NCBI

113 

Kong H, Zhao H, Chen T, Song Y and Cui Y: Targeted P2X7/NLRP3 signaling pathway against inflammation, apoptosis, and pyroptosis of retinal endothelial cells in diabetic retinopathy. Cell Death Dis. 13:3362022. View Article : Google Scholar : PubMed/NCBI

114 

Antonetti DA, Silva PS and Stitt AW: Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol. 17:195–206. 2021. View Article : Google Scholar : PubMed/NCBI

115 

Wang X, Ye J and Liu W: GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice. J Army Med Univ. 46:1369–1377. 2024.

116 

Kaur C, Foulds W and Ling E: Blood-retinal barrier in hypoxic ischaemic conditions: Basic concepts, clinical features and management. Prog Retin Eye Res. 27:622–647. 2008. View Article : Google Scholar : PubMed/NCBI

117 

Puebla M, Tapia PJ and Espinoza H: Key role of astrocytes in postnatal brain and retinal angiogenesis. Int J Mol Sci. 23:26462022. View Article : Google Scholar : PubMed/NCBI

118 

Navarro HI, Daly AE, Rodriguez B, Wu S, Ngo KA, Fraser A, Schiffman A, Liu Y, Smale ST, Chia JJ and Hoffmann A: NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters. Cell Discov. 11:132025. View Article : Google Scholar

119 

Acioglu C and Elkabes S: Innate immune sensors and regulators at the blood brain barrier: Focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation. J Neuroinflammation. 22:392025. View Article : Google Scholar : PubMed/NCBI

120 

Song Y, Dou H, Gong W, Liu X, Yu Z, Li E, Tan R and Hou Y: Bis-N-norgliovictin, a small-molecule compound from marine fungus, inhibits LPS-induced inflammation in macrophages and improves survival in sepsis. Eur J Pharmacol. 705:49–60. 2013. View Article : Google Scholar : PubMed/NCBI

121 

Abcouwer SF: Neural inflammation and the microglial response in diabetic retinopathy. J Ocul Biol Dis Infor. 4:25–33. 2012. View Article : Google Scholar :

122 

Sun H, Ma X, Ma H, Li S, Xia Y, Yao L, Wang Y, Pang X, Zhong J, Yao G, et al: High glucose levels accelerate atherosclerosis via NLRP3-IL/MAPK/NF-κB-related inflammation pathways. Biochem Biophys Res Commun. 704:1497022024. View Article : Google Scholar

123 

He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW and Li B: Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 6:4252021. View Article : Google Scholar : PubMed/NCBI

124 

Chidiac R, Zhang Y, Tessier S, Faubert D, Delisle C and Gratton JP: Comparative phosphoproteomics analysis of VEGF and angiopoietin-1 signaling reveals ZO-1 as a critical regulator of endothelial cell proliferation. Mol Cell Proteom. 15:1511–1525. 2016. View Article : Google Scholar

125 

Greene C, Hanley N and Campbell M: Claudin-5: Gatekeeper of neurological function. Fluids Barriers CNS. 16:32019. View Article : Google Scholar : PubMed/NCBI

126 

Zhao H, Lv Y, Xu J, Song X, Wang Q, Zhai X, Ma X, Qiu J, Cui L and Sun Y: The activation of microglia by the complement system in neurodegenerative diseases. Ageing Res Rev. 104:1026362025. View Article : Google Scholar

127 

Ricklin D, Hajishengallis G, Yang K and Lambris JD: Complement: A key system for immune surveillance and homeostasis. Nat Immunol. 11:785–797. 2010. View Article : Google Scholar : PubMed/NCBI

128 

Ayyubova G and Madhu LN: Microglial NLRP3 inflammasomes in Alzheimer's disease pathogenesis: From interaction with autophagy/mitophagy to therapeutics. Mol Neurobiol. 62:7124–7143. 2025. View Article : Google Scholar : PubMed/NCBI

129 

Yanai R, Thanos A and Connor KM: Complement involvement in neovascular ocular diseases. Adv Exp Med Biol. 946:161–183. 2012. View Article : Google Scholar

130 

Padmakumar L, Menon RN, Gopala S and Vilanilam GC: MTH1 in the disorders of the central nervous system: Scope beyond brain tumors and challenges. Acta Neurol Belg. Feb 17–2025.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

131 

Chung J, Jernigan J, Menees KB and Lee JK: RGS10 mitigates high glucose-induced microglial inflammation via the reactive oxidative stress pathway and enhances synuclein clearance in microglia. Front Cell Neurosci. 18:13742982024. View Article : Google Scholar : PubMed/NCBI

132 

Homme RP, Sandhu HS, George AK, Tyagi SC and Singh M: Sustained inhibition of NF-κB activity mitigates retinal vasculopathy in diabetes. Am J Pathol. 191:947–964. 2021. View Article : Google Scholar : PubMed/NCBI

133 

Park SS: Retinal glia and NF-κB in diabetic retinopathy pathogenesis. Ann Transl Med. 11:3072023. View Article : Google Scholar

134 

Chen W, Wu Z, Cheng Z, Zhang Y, Luo Q and Yin M: HO-1 represses NF-κB signaling pathway to mediate microglia polarization and phagocytosis in intracerebral hemorrhage. Neuroscience. 566:17–27. 2025. View Article : Google Scholar

135 

Gonzalez-Cortes JH, Martinez-Pacheco VA, Gonzalez-Cantu JE, Bilgic A, de Ribot FM, Sudhalkar A, Mohamed-Hamsho J, Kodjikian L and Mathis T: Current treatments and innovations in diabetic retinopathy and diabetic macular edema. Pharmaceutics. 15:1222022. View Article : Google Scholar

136 

Mounirou BAM, Adam ND, Yakoura AKH, Aminou MSM, Liu YT and Tan LY: Diabetic retinopathy: An overview of treatments. Indian J Endocrinol Metab. 26:111–118. 2022. View Article : Google Scholar : PubMed/NCBI

137 

Arrigo A, Aragona E and Bandello F: VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy. Ann Med. 54:1089–1111. 2022. View Article : Google Scholar : PubMed/NCBI

138 

Zhang W, Geng J and Sang A: Effectiveness of panretinal photocoagulation plus intravitreal anti-VEGF treatment against PRP alone for diabetic retinopathy: A systematic review with meta-analysis. Front Endocrinol (Lausanne). 13:8076872022. View Article : Google Scholar : PubMed/NCBI

139 

Shukla UV and Tripathy K: Diabetic retinopathy. StatPearls [Internet]. StatPearls Publishing; Treasure Island, FL: 2025

140 

Vergmann AS, Nguyen TT, Lee Torp T, Kawasaki R, Wong TY, Peto T and Grauslund J: Efficacy and side effects of individualized panretinal photocoagulation. Ophthalmol Retina. 4:642–644. 2020. View Article : Google Scholar : PubMed/NCBI

141 

Xu W, Cheng W, Cui X and Xu G: Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: Bone marrow-derived mesenchymal stem cells versus Conbercept. BMC Ophthalmol. 20:72020. View Article : Google Scholar : PubMed/NCBI

142 

Martinez-Alejo JM, Baiza-Duran LM and Quintana-Hau JDD: Novel therapies for proliferative retinopathies. Ther Adv Chronic Dis. 13:204062232211403952022. View Article : Google Scholar : PubMed/NCBI

143 

Xu W, Hu Z, Lv Y, Dou G, Zhang Z, Wang H and Wang Y: Microglial density determines the appearance of pathological neovascular tufts in oxygen-induced retinopathy. Cell Tissue Res. 374:25–38. 2018. View Article : Google Scholar : PubMed/NCBI

144 

Qin S, Zhang C, Qin H, Xie H, Luo D, Qiu Q, Liu K and Zhang J, Xu G and Zhang J: Hyperreflective foci and subretinal fluid are potential imaging biomarkers to evaluate anti-VEGF effect in diabetic macular edema. Front Physiol. 12:7914422021. View Article : Google Scholar

145 

Rojo Arias JE, Englmaier VE and Jászai J: VEGF-trap modulates retinal inflammation in the murine oxygen-induced retinopathy (OIR) model. Biomedicines. 10:2012022. View Article : Google Scholar : PubMed/NCBI

146 

Palmhof M, Lohmann S, Schulte D, Stute G, Wagner N, Dick HB and Joachim SC: Fewer functional deficits and reduced cell death after ranibizumab treatment in a retinal ischemia model. Int J Mol Sci. 19:16362018. View Article : Google Scholar : PubMed/NCBI

147 

Xu Y, Lu X, Hu Y, Yang B, Tsui CK, Yu S, Lu L and Liang X: Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1α-VEGF pathway in oxygen-induced retinopathy mice. J Pineal Res. 64:e124732018. View Article : Google Scholar

148 

Wang JH, Lin FL, Chen J, Zhu L, Chuang YF, Tu L, Ma C, Ling D, Hewitt AW, Tseng CL, et al: TAK1 blockade as a therapy for retinal neovascularization. Pharmacol Res. 187:1066172023. View Article : Google Scholar

149 

Church KA, Rodriguez D, Mendiola AS, Vanegas D, Gutierrez IL, Tamayo I, Amadu A, Velazquez P, Cardona SM, Gyoneva S, et al: Pharmacological depletion of microglia alleviates neuronal and vascular damage in the diabetic CX3CR1-WT retina but not in CX3CR1-KO or hCX3CR1I249/M280-expressing retina. Front Immunol. 14:11307352023. View Article : Google Scholar

150 

Church KA, Rodriguez D, Vanegas D, Gutierrez IL, Cardona SM, Madrigal JLM, Kaur T and Cardona AE: Models of microglia depletion and replenishment elicit protective effects to alleviate vascular and neuronal damage in the diabetic murine retina. J Neuroinflammation. 19:3002022. View Article : Google Scholar : PubMed/NCBI

151 

Zhao F, Gao X, Ge X, Cui J and Liu X: Cyanidin-3-o-glucoside (C3G) inhibits vascular leakage regulated by microglial activation in early diabetic retinopathy and neovascularization in advanced diabetic retinopathy. Bioengineered. 12:9266–9278. 2021. View Article : Google Scholar : PubMed/NCBI

152 

Yang B, Xu Y, Yu S, Huang Y, Lu L and Liang X: Anti-angiogenic and anti-inflammatory effect of Magnolol in the oxygen-induced retinopathy model. Inflamm Res. 65:81–93. 2016. View Article : Google Scholar

153 

Tang X, Cui K, Lu X, Wu P, Yu S, Yang B, Xu Y and Liang X: A novel hypoxia-inducible factor 1α inhibitor KC7F2 attenuates oxygen-induced retinal neovascularization. Invest Ophthalmol Vis Sci. 63:132022. View Article : Google Scholar

154 

Song GJ and Suk K: Pharmacological modulation of functional phenotypes of microglia in neurodegenerative diseases. Front Aging Neurosci. 9:1392017. View Article : Google Scholar : PubMed/NCBI

155 

Sun X, Ma L, Li X, Wang J, Li Y and Huang Z: Ferulic acid alleviates retinal neovascularization by modulating microglia/macrophage polarization through the ROS/NF-κB axis. Front Immunol. 13:9767292022. View Article : Google Scholar

156 

Wang Y, Chang T, Wu T, Xu W, Dou G, Wang Y and Guo C: M2 macrophages promote vasculogenesis during retinal neovascularization by regulating bone marrow-derived cells via SDF-1/VEGF. Cell Tissue Res. 380:469–486. 2020. View Article : Google Scholar : PubMed/NCBI

157 

Zhou Y, Yoshida S, Nakao S, Yoshimura T, Kobayashi Y, Nakama T, Kubo Y, Miyawaki K, Yamaguchi M, Ishikawa K, et al: M2 macrophages enhance pathological neovascularization in the mouse model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 56:4767–4777. 2015. View Article : Google Scholar : PubMed/NCBI

158 

Caldwell RW, Rodriguez PC, Toque HA, Narayanan SP and Caldwell RB: Arginase: A multifaceted enzyme important in health and disease. Physiol Rev. 98:641–665. 2018. View Article : Google Scholar : PubMed/NCBI

159 

Monticelli LA, Buck MD, Flamar AL, Saenz SA, Tait Wojno ED, Yudanin NA, Osborne LC, Hepworth MR, Tran SV, Rodewald HR, et al: Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation. Nat Immunol. 17:656–665. 2016. View Article : Google Scholar : PubMed/NCBI

160 

Chen T, Huang X, Zhao YX, Zhou ZW and Zhou WS: NEAT1 inhibits the angiogenic activity of cerebral arterial endothelial cells by inducing the M1 polarization of microglia through the AMPK signaling pathway. Cell Mol Biol Lett. 29:622024. View Article : Google Scholar : PubMed/NCBI

161 

Niu G and Chen X: Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 11:1000–1017. 2010. View Article : Google Scholar : PubMed/NCBI

162 

Cho H, Kambhampati SP, Lai MJ, Zhou L, Lee G, Xie Y, Hui Q, Kannan RM and Duh EJ: Dendrimer-triamcinolone acetonide reduces neuroinflammation, pathological angiogenesis, and neuroretinal dysfunction in ischemic retinopathy. Adv Ther (Weinh). 4:20001812021. View Article : Google Scholar : PubMed/NCBI

163 

Fan W, Huang W, Chen J, Li N, Mao L and Hou S: Retinal microglia: Functions and diseases. Immunology. 166:268–286. 2022. View Article : Google Scholar : PubMed/NCBI

164 

Wang S, Zhang J, Chen J, Tang L, Ke M, Xue Y, He Y, Gong Y and Li Z: ω-3PUFAs inhibit hypoxia-induced retinal neovascularization via regulating microglial pyroptosis through METTL14-mediated m6A modification of IFNB1 mRNA. Appl Biochem Biotechnol. 196:5936–5952. 2024. View Article : Google Scholar : PubMed/NCBI

165 

Mei X, Zhou L, Zhang T, Lu B, Sheng Y and Ji L: Chlorogenic acid attenuates diabetic retinopathy by reducing VEGF expression and inhibiting VEGF-mediated retinal neoangiogenesis. Vasc Pharmacol. 101:29–37. 2018. View Article : Google Scholar

166 

Yu Z, Zhang T, Gong C, Sheng Y, Lu B, Zhou L, Ji L and Wang Z: Erianin inhibits high glucose-induced retinal angiogenesis via blocking ERK1/2-regulated HIF-1α-VEGF/VEGFR2 signaling pathway. Sci Rep. 6:343062016. View Article : Google Scholar

167 

Zhao K, Jiang Y, Zhang J, Shi J, Zheng P, Yang C and Chen Y: Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway. Cell Cycle. 21:2091–2108. 2022. View Article : Google Scholar : PubMed/NCBI

168 

Guo L, Choi S, Bikkannavar P and Cordeiro MF: Microglia: Key players in retinal ageing and neurodegeneration. Front Cell Neurosci. 16:8047822022. View Article : Google Scholar : PubMed/NCBI

169 

Shao F, Wang X, Wu H, Wu Q and Zhang J: Microglia and neuroinflammation: Crucial pathological mechanisms in traumatic brain injury-induced neurodegeneration. Front Aging Neurosci. 14:8250862022. View Article : Google Scholar : PubMed/NCBI

170 

Gao C, Jiang J, Tan Y and Chen S: Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets. Signal Transduct Target Ther. 8:3592023. View Article : Google Scholar : PubMed/NCBI

171 

Yang I, Han SJ, Kaur G, Crane C and Parsa AT: The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci. 17:6–10. 2010. View Article : Google Scholar

172 

Masuda T, Sankowski R, Staszewski O and Prinz M: Microglia heterogeneity in the single-cell era. Cell Rep. 30:1271–1281. 2020. View Article : Google Scholar : PubMed/NCBI

173 

Jiao W, Ji J, Li F, Guo J, Zheng Y, Li S and Xu W: Activation of the Notch-Nox4-reactive oxygen species signaling pathway induces cell death in high glucose-treated human retinal endothelial cells. Mol Med Rep. 19:667–677. 2019.

174 

Seo H, Park SJ and Song M: Diabetic retinopathy (DR): Mechanisms, current therapies, and emerging strategies. Cells. 14:3762025. View Article : Google Scholar : PubMed/NCBI

175 

Radwan SES, El-Kamel A, Zaki EI, Burgalassi S, Zucchetti E and El-Moslemany RM: Hyaluronic-coated albumin nanoparticles for the non-invasive delivery of apatinib in diabetic retinopathy. Int J Nanomedicine. 16:4481–4494. 2021. View Article : Google Scholar : PubMed/NCBI

176 

Wang S, Yang H, Zheng J, Tong A, Mu S, Wang D, Zhao M and Li J: Recent advances and prospects of nanoparticle-based drug delivery for diabetic ocular complications. Theranostics. 15:3551–3570. 2025. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bai Y, Wang X, Qi F, Zuo X and Zou G: Mechanisms of action of retinal microglia in diabetic retinopathy (Review). Int J Mol Med 56: 202, 2025.
APA
Bai, Y., Wang, X., Qi, F., Zuo, X., & Zou, G. (2025). Mechanisms of action of retinal microglia in diabetic retinopathy (Review). International Journal of Molecular Medicine, 56, 202. https://doi.org/10.3892/ijmm.2025.5643
MLA
Bai, Y., Wang, X., Qi, F., Zuo, X., Zou, G."Mechanisms of action of retinal microglia in diabetic retinopathy (Review)". International Journal of Molecular Medicine 56.6 (2025): 202.
Chicago
Bai, Y., Wang, X., Qi, F., Zuo, X., Zou, G."Mechanisms of action of retinal microglia in diabetic retinopathy (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 202. https://doi.org/10.3892/ijmm.2025.5643
Copy and paste a formatted citation
x
Spandidos Publications style
Bai Y, Wang X, Qi F, Zuo X and Zou G: Mechanisms of action of retinal microglia in diabetic retinopathy (Review). Int J Mol Med 56: 202, 2025.
APA
Bai, Y., Wang, X., Qi, F., Zuo, X., & Zou, G. (2025). Mechanisms of action of retinal microglia in diabetic retinopathy (Review). International Journal of Molecular Medicine, 56, 202. https://doi.org/10.3892/ijmm.2025.5643
MLA
Bai, Y., Wang, X., Qi, F., Zuo, X., Zou, G."Mechanisms of action of retinal microglia in diabetic retinopathy (Review)". International Journal of Molecular Medicine 56.6 (2025): 202.
Chicago
Bai, Y., Wang, X., Qi, F., Zuo, X., Zou, G."Mechanisms of action of retinal microglia in diabetic retinopathy (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 202. https://doi.org/10.3892/ijmm.2025.5643
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team