Ganglion cell-derived LysoPS induces retinal neovascularisation by activating the microglial GPR34-PI3K-AKT-NINJ1 axis.
Animals
Microglia
/ metabolism
Mice
Retinal Ganglion Cells
/ metabolism
Retinal Neovascularization
/ metabolism
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases
/ metabolism
Signal Transduction
/ physiology
Proto-Oncogene Proteins c-akt
/ metabolism
Lysophospholipids
/ metabolism
Nerve Growth Factors
/ metabolism
Humans
Male
GPR34
LysoPS
Microglial extracellular traps
NINJ1
PI3K-AKT
Retinal neovascularisation
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
14
08
2024
accepted:
18
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Retinal neovascularisation is a major cause of blindness in patients with proliferative diabetic retinopathy (PDR). It is mediated by the complex interaction between dysfunctional ganglion cells, microglia, and vascular endothelial cells. Notably, retinal microglia, the intrinsic immune cells of the retina, play a crucial role in the pathogenesis of retinopathy. In this study, we found that lysophosphatidylserines (LysoPS) released from injured ganglion cells induced microglial extracellular trap formation and retinal neovascularisation. Mechanistically, LysoPS activated the GPR34-PI3K-AKT-NINJ1 signalling axis by interacting with the GPR34 receptor on the microglia. This activation upregulated the expression of inflammatory cytokines, such as IL-6, IL-8, VEGFA, and FGF2, and facilitated retinal vascular endothelial cell angiogenesis. As a result, inhibition of the GPR34-PI3K-AKT-NINJ1 axis significantly decreased microglial extracellular trap formation and neovascularisation by suppressing LysoPS-induced microglial inflammatory responses, both in vitro and in vivo. This study reveals the crucial role of apoptotic ganglion cells in activating microglial inflammation in PDR, thereby enhancing our understanding of the pathogenesis of retinal neovascularisation.
Identifiants
pubmed: 39468551
doi: 10.1186/s12974-024-03265-7
pii: 10.1186/s12974-024-03265-7
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Lysophospholipids
0
Nerve Growth Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
278Subventions
Organisme : National Natural Science Foundation of China Research Grants
ID : Nos. 82271107
Informations de copyright
© 2024. The Author(s).
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