Distinguished Functions of Microglia in the Two Stages of Oxygen-Induced Retinopathy: A Novel Target in the Treatment of Ischemic Retinopathy

Zhou, Ziyi; Jing, Yutong; Niu, Yali; Chang, Tianfang; Sun, Jiaxing; Guo, Changmei; Wang, Yusheng; Dou, Guo‐Rui

doi:10.3390/life12101676

Cited by 6 publications

(3 citation statements)

References 50 publications

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“…For microglia removal, colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 (Selleck, Shanghai, China) was given daily with oral gavage to OIR mice from P12, as described before. Pups were anesthetized and killed at P17 [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Microglia-Derived Spp1 Promotes Pathological Retinal Neovascularization via Activating Endothelial Kit/Akt/mTOR Signaling

Bai

Wang²,

Yan

et al. 2023

JPM

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Pathological retinal neovascularization (RNV) is the main character of ischemic ocular diseases, which causes severe visual impairments. Though retinal microglia are well acknowledged to play important roles in both physiological and pathological angiogenesis, the molecular mechanisms by which microglia communicates with endothelial cells (EC) remain unknown. In this study, using single-cell RNA sequencing, we revealed that the pro-inflammatory secreted protein Spp1 was the most upregulated gene in microglia in the mouse model of oxygen-induced retinopathy (OIR). Bioinformatic analysis showed that the expression of Spp1 in microglia was respectively regulated via nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor 1α (HIF-1α) pathways, which was further confirmed through in vitro assays using BV2 microglia cell line. To mimic microglia-EC communication, the bEnd.3 endothelial cell line was cultured with conditional medium (CM) from BV2. We found that adding recombinant Spp1 to bEnd.3 as well as treating with hypoxic BV2 CM significantly enhanced EC proliferation and migration, while Spp1 neutralizing blocked those CM-induced effects. Moreover, RNA sequencing of BV2 CM-treated bEnd.3 revealed a significant downregulation of Kit, one of the type III tyrosine kinase receptors that plays a critical role in cell growth and activation. We further revealed that Spp1 increased phosphorylation and expression level of Akt/mTOR signaling cascade, which might account for its pro-angiogenic effects. Finally, we showed that intravitreal injection of Spp1 neutralizing antibody attenuated pathological RNV and improved visual function. Taken together, our work suggests that Spp1 mediates microglia-EC communication in RNV via activating endothelial Kit/Akt/mTOR signaling and is a potential target to treat ischemic ocular diseases.

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Section: Methodsmentioning

confidence: 99%

Microglia-Derived Spp1 Promotes Pathological Retinal Neovascularization via Activating Endothelial Kit/Akt/mTOR Signaling

Bai

Wang²,

Yan

et al. 2023

JPM

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“…In contrast, the intravitreal injection of bone marrow-derived M2 macrophages promoted pathological retinal angiogenesis [ 134 ]. PLX-5622 -mediated microglia depletion reduced pathological angiogenesis in OIR [ 135 ]. Systemic macrophage depletion with intraperitoneal clodronate liposomes reduced retinal avascular area and neovascular tufts at P17 after OIR [ 136 ].…”

Section: Myeloid Cells In Retinal Pathological Angiogenesismentioning

confidence: 99%

Role of myeloid cells in ischemic retinopathies: recent advances and unanswered questions

Shahror,

Morris,

Mohammed

et al. 2024

J Neuroinflammation

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Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal pathologies and recent studies suggest that targeting myeloid cells is a promising therapeutic strategy to mitigate diabetic retinopathy and other ischemic retinal diseases. This review summarizes the recent advances in our understanding of the role of microglia and macrophages in retinal diseases and focuses on the effects of myeloid cells on neurovascular injury and angiogenesis in ischemic retinopathies. We highlight gaps in knowledge and advocate for a more detailed understanding of the role of myeloid cells in retinal ischemic injury to fully unlock the potential of targeting myeloid cells as a therapeutic strategy for retinal ischemia.

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“…Similarly, several retinal degenerative diseases associated with elevated GFAP and Müller cell gliosis, including light-induced retinal degeneration, are also associated with increased Gal3 expression [5,101]. Gal3 knockout significantly dampened the reactivity of glial cells and preserved photoreceptor cells and ganglion cells [71,109]. Therefore, it could be concluded that in the absence of Gal3, a mere 30% decrease in cerebral blood flow itself would not result in any significant retinal damage.…”

Section: Retinal Degenerative Diseasementioning

confidence: 99%

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target

Zhou,

Feng,

Sun

et al. 2023

IJMS

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Galectin-3 is the most studied member of the Galectin family, with a large range of mediation in biological activities such as cell growth, proliferation, apoptosis, differentiation, cell adhesion, and tissue repair, as well as in pathological processes such as inflammation, tissue fibrosis, and angiogenesis. As is known to all, inflammation, aberrant cell apoptosis, and neovascularization are the main pathophysiological processes in retinal degeneration and many ocular diseases. Therefore, the review aims to conclude the role of Gal3 in the retinal degeneration of various diseases as well as the occurrence and development of the diseases and discuss its molecular mechanisms according to research in systemic diseases. At the same time, we summarized the predictive role of Gal3 as a biomarker and the clinical application of its inhibitors to discuss the possibility of Gal3 as a novel target for the treatment of ocular diseases.

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Distinguished Functions of Microglia in the Two Stages of Oxygen-Induced Retinopathy: A Novel Target in the Treatment of Ischemic Retinopathy

Cited by 6 publications

References 50 publications

Microglia-Derived Spp1 Promotes Pathological Retinal Neovascularization via Activating Endothelial Kit/Akt/mTOR Signaling

Microglia-Derived Spp1 Promotes Pathological Retinal Neovascularization via Activating Endothelial Kit/Akt/mTOR Signaling

Role of myeloid cells in ischemic retinopathies: recent advances and unanswered questions

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target

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