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. 2024 Mar 7;21:65. doi: 10.1186/s12974-024-03058-y

Table 3.

Summary of Key Studies Highlighting the Role of Myeloid Cells in Ischemic Retinopathies

Study Model Species Outcomes and measures
Acute ischemic retinopathy
 Wagner et al. (2021) [99] IR Rat Microglial activation enhances pro-inflammatory cytokines accompanied by TLR signaling 2 h post-IR (p = 0.028)
 Abcouwer et al. (2021) [75] IR Mouse Myeloid leukocyte accumulation 14 days post-IR (p ≤ 0.001)
 Tang et al. (2020) [82] IR Mouse Elevated Iba1+ cells numbers in retina 1-day post-IR (p < 0.001)
 Fouda et al. (2018) [46] IR Mouse Myeloid arginase 1 deletion exacerbates loss of retinal neurons (p < 0.05) and thinning of the retina at 7 days post-IR (p < 0.05)
 Ahmed et al. (2017) [73] IR Mouse Increased number of IBA1+ cells/mm in GCL at 1-day post-IR (p ≤ 0.0001)
 Sanchez et al. (2003) [108] IR Rat Increased expression of IL-6 by microglia/macrophages at 2 h post-IR (p < 0.05)
Diabetic retinopathy
 Huang et al. (2023) [118] SIDR Mouse Retinal microglia necroptosis promotes neuroinflammation in the early stages of diabetic retinopathy
 Park et al. (2021) [116] SIDR Rat Increased Iba1+ retinal microglia density in diabetic mice compared to control mice (p < 0.05)
 Atawia et al. (2020) [115] WDIDR Mouse Arginase 2 (A2) deletion inhibits retinal microglia activation (p < 0.05)
 Mendiola et al. (2016) [124] Ins2Akita Mouse Recombinant fractalkine reduces perivascular microglial clustering (p < 0.01)
 Cardona et al. (2015) [123] Ins2Akita Mouse Retinal microglia increase in diabetic mice (p < 0.05)
 Rangasamy et al. (2014) [121] SIDR Rat CCL2 activates retinal microglia and attenuates vascular leakage and infiltration of monocytes
 Krady et al. (2005) [117] SIDR Rat Microglia activate in the early stages of diabetic retinopathy
Pathological retinal angiogenesis
 Liu et al. (2022) [156] OIR Mouse Localization of microglia near pathological neovascular tufts (p < 0.001)
 Liu et al. (2022) [138] OIR Mouse Macrophage depletion by clodronate increases neovascularization on P12 (p < 0.05)
 Zhou et al. (2022) [135] OIR Mouse Microglial depletion suppresses pathological neovascularization (p < 0.05)
 He et al. (2021) [119] OIR Mouse Microglia necroptosis largely ablates retinal angiogenesis
 Liu et al. (2020) [142] OIR Mouse Arginase-1 transcript is elevated in microglia/macrophages (p < 0.001)
 Villacampa et al. (2020) [144] OIR Mouse Depletion of myeloid-cell specific Vhl stabilizes HIFs and stimulates retinal revascularization (p < 0.05; p < 0.001)
 Zhu et al. (2017) [133] OIR Mouse M2 macrophage polarization genes are upregulated on P13-P24 (p < 0.05)
 Gao et al. (2016) [136] OIR Mouse Macrophage depletion by clodronate reduces percentage of neovascular area (p < 0.01)
 Zhou et al. (2015) [134] OIR Mouse Bone marrow-derived M2 macrophages increase pathological neovascularization (p < 0.01)
 Dejda et al. (2014) [146] OIR Mouse NRP-1+ myeloid cells are recruited to neovascularization sites in the retina
 Zhou et al. (2015) [134] OIR Mouse Bone marrow-derived M2 macrophages increase pathological neovascularization (p < 0.01)
 Kataoka et al. (2011) [137] OIR Mouse Depletion of native vitreal macrophages reduces neovascularization (p < 0.01)
Human ischemic retinopathy
 Ong et al. (2021) [149] DR Human Increased density of macrophage-like cells in PDR compared to healthy patients (p < 0.05)
 Zeng et al. (2008) [150] DR Human Microglial cells were observed to cluster around veins in the GCL, microaneurysms, and retinal and vitreal neovascularization

CCL2: Monocyte chemoattractant protein-1, DR: Diabetic retinopathy, FABP5: Fatty acid-binding protein 5, GCL: Ganglion cell layer, HIF: Hypoxia-inducible factor, IR: ischemia reperfusion, NRP-1: Neuropilin-1, OIR: Oxygen-induced retinopathy, PDR: proliferative diabetic retinopathy, PKM2: enzyme pyruvate kinase M2, SIDR: Streptozotocin-induced diabetic retinopathy, TLR: Toll-like receptor, Vhl: Von Hippel-Lindau tumor suppressor protein, WDIDR: Western-diet induced retinopathy