The Interaction Between Microglia and Macroglia in Glaucoma

Zhao, Xiaohuan; Sun, Rou; Luo, Xueting; Wang, Rui; Sun, Xiaodong

doi:10.3389/fnins.2021.610788

Cited by 31 publications

(29 citation statements)

References 111 publications

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“…Several studies in animal models and patients with glaucoma [71][72][73] have found that astrocytes and Müller glia cells become reactive at early stages of glaucomatous conditions when RGCs are intact, suggesting a role for macroglia in the initiation and progression of glaucoma. The POAG genes driving the astrocyte enrichment included genes enriched in extracellular matrix organization (COL8A2, COL11A1), TGF-beta signaling (SMAD6) and sterol or lipid binding (DGKG, MOV10, RORA) (Supplementary Table [34][35].…”

Section: Discussionmentioning

confidence: 99%

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Hamel

Rouhana

Yan

et al. 2022

Preprint

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Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide; however the molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization analysis of >130 POAG and 112 IOP GWAS loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina proposed causal genes for 60% of the loci, that were enriched in extracellular matrix organization, cell adhesion, and vascular development. Analyzing single-nucleus RNA-seq of glaucoma-relevant eye tissues, we found that the colocalizing genes were enriched in known and less well-characterized cell types, including fibroblasts in the conventional and unconventional aqueous outflow pathways; vascular cells in the anterior segment; astrocytes and Müller glia in retina and optic nerve head (ONH); and smooth muscle and vascular endothelial cells in ONH. This study nominated IOP- dependent and independent regulatory mechanisms, genes, and cell types that may underlie POAG pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Hamel

Rouhana

Yan

et al. 2022

Preprint

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“…Animal models of acute OHT suggest that a predominant M1/A1 type of microglial cells and astrocytes in the acute phase contributes to the early proinflammatory state, which may subside thereafter. The dynamic turnover and interplay between microglial and macroglial cells in glaucoma set the background of retinal inflammation, which is reviewed in detail by Zhao et al ( 110 ).…”

Section: Retinal Gliosis and Interplay With T Cellsmentioning

confidence: 99%

T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration

Wang

Wei

2021

Front. Immunol.

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Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.

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“…These cells offer metabolic support to neurons, neuroprotection and regulate the synaptic activity. Microglial cells are CNS-resident innate immune cells, migratory blood monocytes to the CNS that retain monocyte-specific antigens CD11b/c, complement peptide C3a receptor 1 (C3aR1) and chemokine receptor (CX3CR1) [28,34]. The activation of microglia is an early event in the retina and optic nerve during glaucoma.…”

Section: Neuroinflammationmentioning

confidence: 99%

The Future of Stem Cells and Their Derivates in the Treatment of Glaucoma. A Critical Point of View

Nicoară

Brie

Jurj

et al. 2021

IJMS

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This review focuses on the clinical translation of preclinical studies, especially those that have used stem cells in the treatment of glaucoma, with an emphasis on optic nerve regeneration. The studies referred to in the review aim to treat optic nerve atrophy, while cell therapies targeting other sites in the eye, such as the trabecular meshwork, have not been addressed. Such complex and varied pathophysiological mechanisms that lead to glaucoma may explain the fact that although stem cells have a high capacity of neuronal regeneration, the treatments performed did not have the expected results and the promise offered by animal studies was not achieved. By analyzing the facts associated with failure, important lessons are to be learned: the type of stem cells that are used, the route of administration, the selection of patients eligible for these treatments, additional therapies that support stem cells transplantation and their mode of action, methods of avoiding the host’s immune response. Many of these problems could be solved using exosomes (EV), but also miRNA, which allows more targeted approaches with minimal side effects.

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The Interaction Between Microglia and Macroglia in Glaucoma

Cited by 31 publications

References 111 publications

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration

The Future of Stem Cells and Their Derivates in the Treatment of Glaucoma. A Critical Point of View

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