TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
05
02
2021
revised:
14
06
2021
accepted:
15
06
2021
entrez:
29
6
2021
pubmed:
30
6
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1β levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1β levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.
Identifiants
pubmed: 34183443
pii: 4/8/e202101047
doi: 10.26508/lsa.202101047
pmc: PMC8321671
pii:
doi:
Substances chimiques
Calcium Channels
0
IL1B protein, mouse
0
Interleukin-1beta
0
TPCN2 protein, mouse
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Li et al.
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