ArticleDevelopmental cell2024
Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.
Article in Developmental cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.Molecular therapy. Nucleic acids · 2026Article
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.Ophthalmology science · 2026Review
- Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration.Genome medicine · 2026Article
- Review
- Retinal pigment epithelium pathology in age-related macular degeneration: mitigation with melatonin.Frontiers in medicine · 2026Review
- Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Dysregulated lipid metabolism in a retinal pigment epithelial cell model and serum of patients with age-related macular degeneration.BMC biology · 2025Article
- Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS.Ophthalmology scienceArticle
Corrections and comments
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Authors and funding
14 authors.
Funding
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) and increased secretory phospholipase 2-IIA (sPLA2-IIA) levels. Therapeutically, RPE-specific MMP2 supplementation, RAGE-antagonistic peptide, and a small molecule inhibitor of sPLA2-IIA ameliorated drusen accumulation in AMD/MD iPSC-RPE. Ultimately, this study defines a causal role of the MMP2-DAMP-RAGE-sPLA2-IIA axis in AMD/MDs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.