{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dalvi S"],"funding":["National Eye Institute","NEI NIH HHS","Research to Prevent Blindness","University of Rochester","Cleveland Clinic","National Institutes of Health","University of Rochester School of Medicine and Dentistry","NIH HHS"],"pagination":["3290-3305.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11652237"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(24)"],"pubmed_abstract":["Age-related macular degeneration (AMD) and related macular dystrophies (MDs) primarily affect the retinal pigment epithelium (RPE) in the eye. A hallmark of AMD/MDs that drives later-stage pathologies is drusen. Drusen are sub-RPE lipid-protein-rich extracellular deposits, but how drusen forms and accumulates is not known. We utilized human induced pluripotent stem cell (iPSC)-derived RPE from patients with AMD and three distinct MDs to demonstrate that reduced activity of RPE-secreted matrix metalloproteinase 2 (MMP2) contributes to drusen in multiple maculopathies in a genotype-agnostic manner by instigating sterile inflammation and impaired lipid homeostasis via damage-associated molecular pattern molecule (DAMP)-mediated activation of receptor for advanced glycation end-products (RAGE)"],"journal":["Developmental cell"],"pubmed_title":["Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies."],"pmcid":["PMC11652237"],"funding_grant_id":["P30 EY025585","R01EY027083","R21EY030817","R01EY033192","R21 EY030817","P30EY025585","R01 EY030183","R01EY030183","S10 OD030302","R01 EY027083","R01 EY033192","R01 EY028167","R01EY028167"],"pubmed_authors":["Spencer W","Dalvi S","Chatterjee A","Bhogavalli A","Bharti K","Anand-Apte B","Reuben-Thomas C","Roll M","Kumar LK","Pebay A","Foley N","Singh R","Arduino C","Ortolan D"],"additional_accession":[]},"is_claimable":false,"name":"Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.","description":"Age-related macular degeneration (AMD) and related macular dystrophies (MDs) primarily affect the retinal pigment epithelium (RPE) in the eye. A hallmark of AMD/MDs that drives later-stage pathologies is drusen. Drusen are sub-RPE lipid-protein-rich extracellular deposits, but how drusen forms and accumulates is not known. We utilized human induced pluripotent stem cell (iPSC)-derived RPE from patients with AMD and three distinct MDs to demonstrate that reduced activity of RPE-secreted matrix metalloproteinase 2 (MMP2) contributes to drusen in multiple maculopathies in a genotype-agnostic manner by instigating sterile inflammation and impaired lipid homeostasis via damage-associated molecular pattern molecule (DAMP)-mediated activation of receptor for advanced glycation end-products (RAGE)","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-13T04:47:45.529Z","creation":"2026-06-13T03:08:54.43Z"},"accession":"S-EPMC11652237","cross_references":{"pubmed":["39362220"],"doi":["10.1016/j.devcel.2024.09.006"]}}