Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
NLRP3 inflammasome activation and complement-mediated inflammation have been implicated in promoting choroidal neovascularization (CNV) in age-related macular degeneration (AMD), but central questions regarding their contributions to AMD pathogenesis remain unanswered. Key open questions are (1) whether NLRP3 inflammasome activation mainly in retinal pigment epithelium (RPE) or rather in non-RPE cells promotes CNV, (2) whether inflammasome activation in CNV occurs via NLRP3 or also through NLRP3-independent mechanisms, and (3) whether complement activation induces inflammasome activation in CNV. Here we show in a neovascular AMD mouse model that NLRP3 inflammasome activation in non-RPE cells but not in RPE cells promotes CNV. We demonstrate that both NLRP3-dependent and NLRP3-independent inflammasome activation mechanisms induce CNV. Finally, we find that complement and inflammasomes promote CNV through independent mechanisms. Our findings uncover an unexpected role of non-NLRP3 inflammasomes for CNV and suggest that combination therapies targeting inflammasomes and complement may offer synergistic benefits to inhibit CNV.
Pubmed ID: 33305736
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsMus musculus with name B6.129S6-Nlrp3tm1Bhk/J from IMSR.
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis unknown targets CASPASE 1 P10 (CLEAVED ALA317)
View all literature mentionsThis polyclonal targets Mouse Caspase-1 p10, cleaved
View all literature mentionsThis unknown targets Actin Beta
View all literature mentionsThis unknown targets Non-phospho (Active) β-Catenin (Ser33/37/Thr41) (D13A1) Rabbit mAb
View all literature mentionsThis monoclonal targets P2RY12
View all literature mentionsThis polyclonal targets C5b-9
View all literature mentionsThis polyclonal targets caspase-1 p10
View all literature mentionsThis monoclonal targets Cre Recombinase
View all literature mentions