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Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma.
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- Additional Information
- Source:
Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE
- Publication Information:
Original Publication: [London] : BioMed Central, c2004-
- Subject Terms:
- Abstract:
Background: Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.
Methods: A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca 2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.
Results: We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.
Conclusions: These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
(© 2021. The Author(s).)
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- Grant Information:
81790642 National Natural Science Foundation of China; 31872765 Natural Science Foundation of Tianjin Municipal Science and Technology Commission
- Contributed Indexing:
Keywords: ATP/P2X7 receptor; Activation; Glaucoma; Inflammatory response; Microglia; Müller cells
- Accession Number:
0 (Cytokines)
0 (Receptors, Purinergic P2X7)
8L70Q75FXE (Adenosine Triphosphate)
- Publication Date:
Date Created: 20211225 Date Completed: 20220328 Latest Revision: 20220328
- Publication Date:
20240829
- Accession Number:
PMC8705189
- Accession Number:
10.1186/s12974-021-02366-x
- Accession Number:
34952606
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