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Retinal microglia polarization in diabetic retinopathy

Published online by Cambridge University Press:  03 May 2021

Xin Li ,
Zi-Wei Yu ,
Hui-Yao Li ,
Yue Yuan ,
Xin-Yuan Gao  and
Hong-Yu Kuang
Xin Li
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Zi-Wei Yu
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Hui-Yao Li
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Yue Yuan
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Xin-Yuan Gao*
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Hong-Yu Kuang
Affiliation:
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
*
*Address correspondence to: Xin-Yuan Gao, Email: 15369337970@163.com
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Abstract

Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.

Keywords

microglia polarizationretinal microgliadiabetic retinopathy
Type
Review Article
Information
Visual Neuroscience , Volume 38 , 2021 , E006
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Ali, S.A., Zaitone, S.A., Dessouki, A.A. & Ali, A.A. (2019). Pregabalin affords retinal neuroprotection in diabetic rats: suppression of retinal glutamate, microglia cell expression and apoptotic cell death. Experimental Eye Research 184, 78–90.CrossRefGoogle ScholarPubMed
Altmann, C. & Schmidt, M.H.H. (2018). The role of microglia in diabetic retinopathy: inflammation, microvasculature defects and neurodegeneration. International Journal of Molecular Sciences 19, 110.CrossRefGoogle ScholarPubMed
Álvarez-Sanchez, N., Álvarez-Ríos, A.I., Guerrero, J.M., García-García, F.J., Rodríguez-Mañas, L., Cruz-Chamorro, I., Lardone, P.J. & Carrillo-Vico, A. (2019). Homocysteine and C-reactive protein levels are associated with frailty in older Spaniards: the Toledo study for healthy aging. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 75, 1488–1494.CrossRefGoogle Scholar
Arroba, A.I. & Valverde, Á.M. (2017). Modulation of microglia in the retina: new insights into diabetic retinopathy. Acta diabetologica 54, 527–533.CrossRefGoogle ScholarPubMed
Arroba, A.I., Alcalde-Estevez, E., García-Ramírez, M., Cazzoni, D., de la Villa, P., Sánchez-Fernández, E.M., Mellet, C.O., García Fernández, J.M., Hernández, C., Simó, R. & Valverde, Á.M. (2016). Modulation of microglia polarization dynamics during diabetic retinopathy in db/db mice. Biochimica et biophysica acta 1862, 1663–1674.CrossRefGoogle ScholarPubMed
Baya Mdzomba, J., Joly, S., Rodriguez, L., Dirani, A., Lassiaz, P., Behar-Cohen, F. & Pernet, V. (2020). Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury. Cell Death & Disease 11, 101.CrossRefGoogle ScholarPubMed
Bok, S., Kim, Y.E., Woo, Y., Kim, S., Kang, S.J., Lee, Y., Park, S.K., Weissman, I.L. & Ahn, G.O. (2017). Hypoxia-inducible factor-1α regulates microglial functions affecting neuronal survival in the acute phase of ischemic stroke in mice. Oncotarget 8, 111508–111521.CrossRefGoogle ScholarPubMed
Chan, W.Y., Kohsaka, S. & Rezaie, P. (2007). The origin and cell lineage of microglia: new concepts. Brain Research Reviews 53, 344–354.CrossRefGoogle ScholarPubMed
Chang, K.C., Ponder, J., LaBarbera, D.V. & Petrash, J.M. (2014). Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia. Investigative Ophthalmology & Visual Science 55, 2853–2861.CrossRefGoogle ScholarPubMed
Choudhary, R., Kapoor, M.S., Singh, A. & Bodakhe, S.H. (2017). Therapeutic targets of renin-angiotensin system in ocular disorders. Journal of Current Ophthalmology 29, 7–16.CrossRefGoogle ScholarPubMed
Cobos Jimenez, V., Bradley, E.J., Willemsen, A.M., van Kampen, Antoine H.C., Baas, F. & Kootstra, N.A. (2014). Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages. Physiological Genomics 46, 91–103.CrossRefGoogle ScholarPubMed
Cucak, H., Grunnet, L.G. & Rosendahl, A. (2014). Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization. Journal of Leukocyte Biology 95, 149–160.CrossRefGoogle ScholarPubMed
Del Rio-Hortega Bereciartu, J. (2019). Pio del Rio-Hortega: The Revolution of Glia. Anat Rec (Hoboken).Google Scholar
Dereki, N.C., Cronk, J.C. & Kipnis, J. (2013). The role of microglia in brain maintenance: implications for Rett syndrome. Trends in Immunology 34, 144–150.CrossRefGoogle Scholar
Dong, N. & Wang, Y. (2019). MiR-30a regulates S100A12-induced retinal microglial activation and inflammation by targeting NLRP3. Current Eye Research 44, 1236–1243.CrossRefGoogle ScholarPubMed
Dong, N., Xu, B., Shi, H. & Lu, Y. (2016). miR-124 regulates amadori-glycated albumin-induced retinal microglial activation and inflammation by targeting Rac1. Investigative Ophthalmology & Visual Science 57, 2522–2532.CrossRefGoogle ScholarPubMed
Elmasry, K., Mohamed, R., Sharma, I., Elsherbiny, N.M., Liu, Y., Al-Shabrawey, M. & Tawfik, A. (2018). Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic retinopathy and age-related macular degeneration. Oncotarget 9, 12562–12590.CrossRefGoogle ScholarPubMed
Elsherbiny, N.M., Sharma, I., Kira, D., Alhusban, S., Samra, Y.A., Jadeja, R., Martin, P., Al-Shabrawey, M. & Tawfik, A. (2020). Homocysteine induces inflammation in retina and brain. Biomolecules 10, 393.CrossRefGoogle ScholarPubMed
Fang, P., Li, X., Shan, H., Saredy, J.J., Cueto, R., Xia, J., Jiang, X., Yang, X.F. & Wang, H. (2019). Ly6C(+) inflammatory monocyte differentiation partially mediates hyperhomocysteinemia-induced vascular dysfunction in type 2 diabetic db/db mice. Arteriosclerosis, Thrombosis, and Vascular Biology 39, 2097–2119.CrossRefGoogle ScholarPubMed
Fletcher, E.L., Phipps, J.A., Ward, M.M., Vessey, K.A. & Wilkinson-Berka, J.L. (2010). The renin-angiotensin system in retinal health and disease: its influence on neurons, glia and the vasculature. Progress in Retinal and Eye Research 29, 284–311.CrossRefGoogle ScholarPubMed
Freilich, R.W., Woodbury, M.E. & Ikezu, T. (2013). Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia. PloS One 8, e79416.CrossRefGoogle ScholarPubMed
Ghesquière, B., Wong, B.W., Kuchnio, A. & Carmeliet, P. (2014). Metabolism of stromal and immune cells in health and disease. Nature 511, 167–176.CrossRefGoogle ScholarPubMed
Girard, C., Liu, S., Adams, D., Lacroix, C., Sinéus, M., Boucher, C., Papadopoulos, V., Rupprecht, R., Schumacher, M. & Groyer, G. (2012). Axonal regeneration and neuroinflammation: roles for the translocator protein 18 kDa. Journal of Neuroendocrinology 24, 71–81.CrossRefGoogle ScholarPubMed
Graeber, M.B., Li, W. & Rodriguez, M.L. (2011). Role of microglia in CNS inflammation. FEBS Letters 585, 3798–3805.CrossRefGoogle ScholarPubMed
Graff, J.W., Dickson, A.M., Clay, G., McCaffrey, A.P. & Wilson, M.E. (2012). Identifying functional microRNAs in macrophages with polarized phenotypes. The Journal of Biological Chemistry 287, 21816–21825.CrossRefGoogle ScholarPubMed
GrandPre, T., Nakamura, F., Vartanian, T. & Strittmatter, S.M. (2000). Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 403, 439–444.CrossRefGoogle ScholarPubMed
Guo, X. & Li, X. (2017). Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats. Molecular Medicine Reports 16, 2030–2036.CrossRefGoogle ScholarPubMed
Hampton, B.M., Schwartz, S.G., Brantley, M.A. & Flynn, H.W. (2015). Update on genetics and diabetic retinopathy. Clinical Ophthalmology 9, 2175–2193.Google ScholarPubMed
Han, X., Chen, X., Chen, S., Luo, Q., Liu, X., He, A., He, S., Qiu, J., Chen, P., Wu, Y., Zhuang, J., Yang, M., Wu, C., Wu, N., Yang, Y., Ge, J., Zhuang, J. & Yu, K.(2020). Tetramethylpyrazine attenuates endotoxin-induced retinal inflammation by inhibiting microglial activation via the TLR4/NF-κB signalling pathway. Biomedicine & Pharmacotherapy 128, 110273.CrossRefGoogle ScholarPubMed
Haschemi, A., Kosma, P., Gille, L., Evans, C.R., Burant, C.F., Starkl, P., Knapp, B., Haas, R., Schmid, J.A., Jandl, C., Amir, S., Lubec, G., Park, J., Esterbauer, H., Bilban, M., Brizuela, L., Pospisilik, J.A., Otterbein, L.E. & Wagner, O. (2012). The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metabolism 15, 813–826.CrossRefGoogle ScholarPubMed
Hu, F., Tong, J., Deng, B., Zheng, J. & Lu, C. (2019). MiR-495 regulates macrophage M1/M2 polarization and insulin resistance in high-fat diet-fed mice via targeting FTO. Pflugers Archiv: European Journal of Physiology 471, 1529–1537.CrossRefGoogle ScholarPubMed
Hugh Perry, V. & Teeling, J. (2013). Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Seminars in Immunopathology 35, 601–612.CrossRefGoogle Scholar
Huvnh, T.P., Mann, S.N. & Mandal, N.A. (2013). Botanical compounds: effects on major eye diseases. Evidence-based complementary and alternative medicine. eCAM 2013, 549174.Google Scholar
Ibrahim, A.S., Mander, S., Hussein, K.A., Elsherbiny, N.M., Smith, S.B., Al-Shabrawey, M. & Tawfik, A. (2016). Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration. Oncotarget 7, 8532–8545.CrossRefGoogle ScholarPubMed
Karlstetter, M., Nothdurfter, C., Aslanidis, A., Moeller, K., Horn, F., Scholz, R., Neumann, H., Weber, B.H., Rupprecht, R. & Langmann, T. (2014). Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. Journal of Neuroinflammation 11, 3.CrossRefGoogle ScholarPubMed
Karlstetter, M., Scholz, R., Rutar, M., Wong, W.T., Provis, J.M. & Langmann, T. (2015). Retinal microglia: just bystander or target for therapy? Progress in Retinal and Eye Research 45, 30–57.CrossRefGoogle ScholarPubMed
Kawamura, H., Kobayashi, M., Li, Q., Yamanishi, S., Katsumura, K., Minami, M., Wu, D.M. & Puro, D.G. (2004). Effects of angiotensin II on the pericyte-containing microvasculature of the rat retina. The Journal of Physiology 561, 671–683.CrossRefGoogle ScholarPubMed
Kelly, B. & O’Neill, L.A. (2015). Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Research 25, 771–784.CrossRefGoogle ScholarPubMed
Kettenmann, H., Kirchhoff, F. & Verkhratsky, A. (2013). Microglia: new roles for the synaptic stripper. Neuron 77, 10–18.CrossRefGoogle ScholarPubMed
Kierdorf, K. & Prinz, M. (2017). Microglia in steady state. The Journal of Clinical Investigation 127, 3201–3209.CrossRefGoogle ScholarPubMed
Kinuthia, U., Wolf, A. & Langmann, T. (2020). Microglia and inflammatory responses in diabetic retinopathy. Frontiers in Immunology 11, 564077.CrossRefGoogle ScholarPubMed
Kong, L., Wang, Z., Liang, X., Wang, Y., Gao, L. & Ma, C. (2019). Monocarboxylate transporter 1 promotes classical microglial activation and pro-inflammatory effect via 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3. Journal of Neuroinflammation 16, 240.CrossRefGoogle ScholarPubMed
Kraakman, M.J., Murphy, A.J., Jandeleit-Dahm, K. & Kammoun, H.L. (2014). Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Frontiers in Immunology 5, 470.CrossRefGoogle ScholarPubMed
Kuhlmann, A.C. & Guilarte, T.R. (2000). Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. Journal of Neurochemistry 74, 1694–1704.CrossRefGoogle ScholarPubMed
Kun-Che, C., Shieh, B. & Petrash, J.M. (2016). Aldose reductase mediates retinal microglia activation. Biochemical and Biophysical Research Communications 473, 565–571.Google Scholar
Kun-Che, C., Shieh, B. & Petrash, J.M. (2019). Role of aldose reductase in diabetes-induced retinal microglia activation. Chemico-Biological Interactions 302, 46–52.Google Scholar
Lampron, A., ElAli, A. & Rivest, S. (2013). Innate immunity in the CNS: redefining the relationship between the CNS and its environment. Neuron 78, 214–232.CrossRefGoogle ScholarPubMed
Liu, X., Zuo, Z., Liu, W., Wang, Z., Hou, Y., Fu, Y. & Han, Y. (2014). Upregulation of Nogo receptor expression induces apoptosis of retinal ganglion cells in diabetic rats. Neural Regeneration Research 9, 815–820.CrossRefGoogle ScholarPubMed
Liu, Z., Luo, H., Zhang, L., Huang, Y., Liu, B., Ma, K., Feng, J., Xie, J., Zheng, J., Hu, J., Zhan, S., Zhu, Y., Xu, Q., Kong, W. & Wang, X. (2012). Hyperhomocysteinemia exaggerates adventitial inflammation and angiotensin II-induced abdominal aortic aneurysm in mice. Circulation Research 111, 1261–1273.CrossRefGoogle ScholarPubMed
Lu, L., Seidel, C.P., Iwase, T., Stevens, R.K., Gong, Y.Y., Wang, X., Hackett, S.F. & Campochiaro, P.A. (2013). Suppression of GLUT1; a new strategy to prevent diabetic complications. Journal of Cellular Physiology 228, 251–257.CrossRefGoogle ScholarPubMed
Ma, W., Zhao, L., Fontainhas, A.M., Fariss, R.N. & Wong, W.T. (2009). Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD. PloS One 4, e7945.CrossRefGoogle ScholarPubMed
Madeira, M.H., Boia, R., Santos, P.F., Ambrósio, A.F. & Santiago, A.R. (2015). Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases. Mediators of Inflammation 2015, 673090.CrossRefGoogle ScholarPubMed
Maeda, J., Higuchi, M., Inaji, M., Ji, B., Haneda, E., Okauchi, T., Zhang, M.R., Suzuki, K. & Suhara, T. (2007). Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor. Brain Research 1157, 100–111.CrossRefGoogle ScholarPubMed
Martinez, F.O., Helming, L. & Gordon, S. (2009). Alternative activation of macrophages: an immunologic functional perspective. Annual Review of Immunology 27, 451–483.CrossRefGoogle ScholarPubMed
Masuda, T., Shimazawa, M. & Hideaki, H. (2017). Retinal diseases associated with oxidative stress and the effects of a free radical scavenger (Edaravone). Oxidative Medicine and Cellular Longevity 2017, 9208489.CrossRefGoogle Scholar
McKimmie, C.S., Roy, D., Forster, T. & Fazakerley, J.K. (2006). Innate immune response gene expression profiles of N9 microglia are pathogen-type specific. Journal of Neuroimmunology 175, 128–141.CrossRefGoogle ScholarPubMed
Mishima, T., Mizuguchi, Y., Kawahigashi, Y., Takizawa, T. & Takizawa, T. (2007). RT-PCR-based analysis of microRNA (miR-1 and -124) expression in mouse CNS. Brain Research 1131, 37–43.CrossRefGoogle ScholarPubMed
Mohamed, R., Sharma, I., Ibrahim, A.S., Saleh, H., Elsherbiny, N.M., Fulzele, S., Elmasry, K., Smith, S.B., Al-Shabrawey, M. & Tawfik, A. (2017). Hyperhomocysteinemia alters retinal endothelial cells barrier function and angiogenic potential via activation of oxidative stress. Scientific Reports 7, 11952.CrossRefGoogle ScholarPubMed
Moreira, T.J.T.P., Pierre, K., Maekawa, F., Repond, C., Cebere, A., Liljequist, S. & Pellerin, L. (2009). Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 29, 1273–1283.CrossRefGoogle Scholar
Nentwich, M.M. & Ulbig, M.W. (2015). Diabetic retinopathy—ocular complications of diabetes mellitus. World Journal of Diabetes 6, 489–499.CrossRefGoogle ScholarPubMed
Obrosova, I.G. & Kador, P.F. (2011). Aldose reductase/polyol inhibitors for diabetic retinopathy. Current Pharmaceutical Biotechnology 12, 373–385.CrossRefGoogle ScholarPubMed
O’Koren, E.G., Yu, C., Klingeborn, M., Wong, A.Y.W., Prigge, C.L., Mathew, R., Kalnitsky, J., Msallam, R.A., Silvin, A., Kay, J.N., Bowes Rickman, C., Arshavsky, V.Y., Ginhoux, F., Merad, M. & Saban, D.R. (2019). Microglial function is distinct in different anatomical locations during retinal homeostasis and degeneration . Immunity 50, 723–737 e7.CrossRefGoogle ScholarPubMed
Phipps, J.A., Vessey, K.A., Brandli, A., Nag, N., Tran, M.X., Jobling, A.I. & Fletcher, E.L. (2018). The role of angiotensin II/AT1 receptor signaling in regulating retinal microglial activation. Investigative Ophthalmology & Visual Science 59, 487–498.CrossRefGoogle ScholarPubMed
Ponomarev, E.D., Maresz, K., Tan, Y. & Dittel, B.N. (2007). CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 27, 10714–10721.CrossRefGoogle ScholarPubMed
Ponomarev, E.D., Veremeyko, T., Barteneva, N., Krichevsky, A.M. & Weiner, H.L. (2011). MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nature Medicine 17, 64–70.CrossRefGoogle Scholar
Ponomarev, E.D., Veremeyko, T. & Weiner, H.L. (2013). MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS. Glia 61, 91–103.CrossRefGoogle ScholarPubMed
Powell, E.D. & Field, R.A. (1964). Diabetic retinopathy and rheumatoid arthritis. Lancet 2, 17–18.CrossRefGoogle ScholarPubMed
Reu, P., Khosravi, A., Bernard, S., Mold, J.E., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Druid, H. & Frisén, J. (2017). The lifespan and turnover of microglia in the human brain. Cell Reports 20, 779–784.CrossRefGoogle ScholarPubMed
Rübsam, A., Parikh, S. & Fort, P. (2018). Role of inflammation in diabetic retinopathy. International Journal of Molecular Sciences 19CrossRefGoogle Scholar
Saijo, K. & Glass, C.K. (2011). Microglial cell origin and phenotypes in health and disease. Nature Reviews Immunology 11, 775–787.CrossRefGoogle ScholarPubMed
Sierra, A., de Castro, F., Del Río-Hortega, J., Rafael Iglesias-Rozas, J., Garrosa, M. & Kettenmann, H. (2016). The “Big-Bang” for modern glial biology: Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. Glia 64, 1801–1840.CrossRefGoogle Scholar
Simo, R. & Hernandez, C. (2014). Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends in Endocrinology and Metabolism: TEM 25, 23–33.CrossRefGoogle ScholarPubMed
Sorrentino, F.S., Allkabes, M., Salsini, G., Bonifazzi, C. & Perri, P. (2016). The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy. Life Science 162, 54–59.CrossRefGoogle ScholarPubMed
Streit, W.J., Graeber, M.B. & Kreutzberg, G.W. (1989). Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. Journal of Neuroimmunology 21, 117–123.CrossRefGoogle ScholarPubMed
Su, F., Yi, H., Xu, L. & Zhang, Z. (2015). Fluoxetine and S-citalopram inhibit M1 activation and promote M2 activation of microglia in vitro. Neuroscience 294, 60–68.CrossRefGoogle ScholarPubMed
Tawfik, A., Mohamed, R., Elsherbiny, N.M., DeAngelis, M.M., Bartoli, M. & Al-Shabrawey, M. (2019). Homocysteine: a potential biomarker for diabetic retinopathy. Journal of Clinical Medicine 8, 121.CrossRefGoogle ScholarPubMed
Tay, T.L., Carrier, M. & Tremblay, M.È. (2019). Physiology of microglia. Advances in Experimental Medicine and Biology 1175, 129–148.CrossRefGoogle ScholarPubMed
Thackeray, J.T., Hupe, H.C., Wang, Y., Bankstahl, J.P., Berding, G., Ross, T.L., Bauersachs, J., Wollert, K.C. & Bengel, F.M. (2018). Myocardial inflammation predicts remodeling and neuroinflammation after myocardial infarction. Journal of the American College of Cardiology 71, 263–275.CrossRefGoogle ScholarPubMed
Wang, M., Wang, X., Zhao, L., Ma, W., Rodriguez, I.R., Fariss, R.N. & Wong, W.T. (2014). Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 34, 3793–3806.CrossRefGoogle ScholarPubMed
Wang, S., Wang, F., Yang, H., Li, R., Guo, H. & Hu, L. (2017). Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization. International Immunopharmacology 50, 22–29.CrossRefGoogle ScholarPubMed
Wang, L., Pavlou, S., Du, X., Bhuckory, M., Xu, H. & Chen, M. (2019). Glucose transporter 1 critically controls microglial activation through facilitating glycolysis. Molecular Neurodegeneration 14, 2.CrossRefGoogle ScholarPubMed
Wang, W., Zhan, R., Zhou, J., Wang, J. & Chen, S. (2018). MiR-10 targets NgR to modulate the proliferation of microglial cells and the secretion of inflammatory cytokines. Experimental and Molecular Pathology 105, 357–363.CrossRefGoogle ScholarPubMed
Wosik, K., Cayrol, R., Dodelet-Devillers, A., Berthelet, F., Bernard, M., Moumdjian, R., Bouthillier, A., Reudelhuber, T.L. & Prat, A. (2007). Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 27, 9032–9042.CrossRefGoogle ScholarPubMed
Wu, Y., Ye, F., Lu, Y., Yong, H., Yin, R., Chen, B. & Yong, Y. (2018). Diosgenin glucoside protects against myocardial injury in diabetic mice by inhibiting RIP140 signaling. American Journal of Translational Research 10, 3742–3749.Google ScholarPubMed
Yang, X., Huo, F., Liu, B., Liu, J., Chen, T., Li, J., Zhu, Z. & Lv, B. (2017). Crocin inhibits oxidative stress and pro-inflammatory response of microglial cells associated with diabetic retinopathy through the activation of PI3K/Akt signaling pathway. Journal of Molecular Neuroscience: MN 61, 581–589.CrossRefGoogle ScholarPubMed
You, Z.P., Zhang, Y.L., Shi, K., Shi, L., Zhang, Y.Z., Zhou, Y. & Wang, C.Y. (2017). Suppression of diabetic retinopathy with GLUT1 siRNA. Scientific Reports 7, 7437.CrossRefGoogle ScholarPubMed
Zeng, X., Ng, Y. & Ling, E. (2000). Neuronal and microglial response in the retina of streptozotocin-induced diabetic rats. Visual Neuroscience 17, 463–471.CrossRefGoogle ScholarPubMed
Zeng, H., Green, W. & Tso, M. (2008). Microglial activation in human diabetic retinopathy. Archives of Ophthalmology (Chicago, Ill: 1960) 126, 227–232.CrossRefGoogle ScholarPubMed
Zhang, X., Yuhong, Y. & Feng, Z. (2018). Suppression of microRNA-495 alleviates high-glucose-induced retinal ganglion cell apoptosis by regulating Notch/PTEN/Akt signaling. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 106, 923–929.CrossRefGoogle ScholarPubMed
Zhang, T., Hao, O., Mei, X., Lu, B., Yu, Z., Chen, K., Wang, Z. & Ji, L. (2019). Erianin alleviates diabetic retinopathy by reducing retinal inflammation initiated by microglial cells via inhibiting hyperglycemia-mediated ERK1/2-NF-κB signaling pathway. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 33, 11776–11790.CrossRefGoogle ScholarPubMed
Zhao, L., Zabel, M.K., Wang, X., Ma, W., Shah, P., Fariss, R.N., Qian, H., Parkhurst, C.N., Gan, W.B. & Wong, W.T. (2015). Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO Molecular Medicine 7, 1179–1197.CrossRefGoogle ScholarPubMed
Zhou, D., Ji, L. & Chen, Y. (2020). TSPO modulates IL-4-induced microglia/macrophage M2 polarization via PPAR-γ pathway. Journal of Molecular Neuroscience 70, 542–549.CrossRefGoogle ScholarPubMed
Zhu, X., Wang, K., Zhang, K., Tan, X., Wu, Z., Sun, S., Zhou, F. & Zhu, L. (2015). Tetramethylpyrazine protects retinal capillary endothelial cells (TR-iBRB2) against IL-1β-induced nitrative/oxidative stress. International Journal of Molecular Sciences 16, 21775–21790.CrossRefGoogle ScholarPubMed