Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

doi:10.14336/ad.2023.0823-3

Cited by 2 publications

(4 citation statements)

References 187 publications

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“…(Zhao et al, 2023). In addition, the crosstalk between microglia, Müller glia and astrocyte plays an important role in AMD pathology process (Cuenca et al, 2014;Zhao et al, 2023). In this study, cell-cell communication analysis showed that Müller glia and astrocyte interact with microglia via secreted SPP1.…”

Section: Discussionmentioning

confidence: 70%

“…Currently, microglia, as one type of neuroglial cells, have been found to closely interact with other cells in both central and peripheral nervous system, which is important for the maintenance of nervous tissues. Notably, it has been suggested that the migration of activated microglia to the ongoing retinal lesion and their phenotype transformation are the hallmarks of AMD pathogenesis ( Zhao et al, 2023 ). In addition, the crosstalk between microglia, Müller glia and astrocyte plays an important role in AMD pathology process ( Cuenca et al, 2014 ; Zhao et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, it has been suggested that the migration of activated microglia to the ongoing retinal lesion and their phenotype transformation are the hallmarks of AMD pathogenesis ( Zhao et al, 2023 ). In addition, the crosstalk between microglia, Müller glia and astrocyte plays an important role in AMD pathology process ( Cuenca et al, 2014 ; Zhao et al, 2023 ). In this study, cell-cell communication analysis showed that Müller glia and astrocyte interact with microglia via secreted SPP1.…”

Section: Discussionmentioning

confidence: 99%

“…AMD, age-related macular degeneration. (Zhao et al, 2023). In addition, the crosstalk between microglia, Müller glia and astrocyte plays an important role in AMD pathology process (Cuenca et al, 2014;Zhao et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration

Lei,

Hu,

Wei

2024

Front. Cell. Neurosci.

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PurposeTo investigate the role of senescence-related cytokines (SRCs) in the pathophysiology of age-related macular degeneration (AMD).DesignThe whole study is based on single-cell and bulk tissue transcriptomic analysis of the human neuroretinas with or without AMD. The transcriptomic data of human neuroretinas was obtained from Gene-Expression Omnibus (GEO) database.MethodsFor single-cell transcriptomic analysis, the gene expression matrix goes through quality control (QC) filtering, being normalized, scaled and integrated for downstream analysis. The further analyses were performed using Seurat R package and CellChat R package. After cell type annotation, the expression of phenotype and functional markers of microglia was investigated and cell-cell communication analysis was performed. For bulk tissue transcriptomic analysis, GSE29801 dataset contains the transcriptomic data of human macular neuroretina (n = 118) from control group and AMD patients. The expression of SPP1 in control and AMD subtypes were compared by Student’s t-test. In addition, the AMD macular neuroretina were classified into SPP1-low and SPP1-high groups according to the expression level of SPP1. The differentially expressed genes between these two groups were subsequently identified and the pathway enrichment analysis for these genes was further conducted.ResultsSecreted phosphoprotein 1, as an SRC, was revealed to be highly expressed in microglia of AMD neuroretina and the SPP1-receptor signaling was highly activated in AMD neuroretina. In addition, SPP1 signaling was associated with the pro-inflammatory phenotype and phagocytic state of microglia. SPP1 expression was elevated in macular neuroretina with late dry and wet AMD and the inflammatory pathways were found to be activated in SPP1-high AMD macular neuroretina.ConclusionOur findings indicated that SPP1 and microglial activation might play an important role in the pathophysiology of AMD. Therefore, SPP1 might serve as a potential therapeutic target for AMD. More in vitro and in vivo studies are required to confirm the results and the therapeutic effect of SPP1-targeting strategy.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration

Lei,

Hu,

Wei

2024

Front. Cell. Neurosci.

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Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration

Zhang,

Wan,

et al. 2024

Preprint

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Background The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration. Methods LD was induced by exposing mice to 4000 lux of light for 2–4 hrs. IBU (100 or 200 mg/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). The cell death genes were analyzed at 24 and 72 hours (hrs) after LD by the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of the key necroptosis gene was assessed by immunohistochemistry. Results Retinal outer nuclear layer (ONL) thickness in the vehicle-injected animals was 8.7 ± 0.6% of retinas without LD (p < 0.0001). In IBU 200mg/kg treated mice, central ONL thickness was 74.9 ± 7.7% of untreated retinas (p < 0.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hrs after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), and C-C motif chemokine ligand 2 (Ccl2) increased by 10, 17 and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including Ripk3 and Mlkl, were upregulated in LD vehicle-treated mice, but dramatically reduced to near the no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12 hrs after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas. Conclusions Systemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.

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Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

Cited by 2 publications

References 187 publications

Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration

Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration

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