ArticleProceedings of the National Academy of Sciences of the United States of America2017
Drusen in patient-derived hiPSC-RPE models of macular dystrophies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 118 citations in OpenAlex.
- 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
- Restoration of impaired lysosomal function mitigates drusen-like deposit formation and cell death in Malattia Leventinese.JCI insight · 2026Article
- Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Review
- Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Article
- Characterization of Bruch's Membrane Formation in Human Fetal Retina and De Novo Membrane Synthesis by hPSC-Derived Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025Article
- Dysregulated lipid metabolism in a retinal pigment epithelial cell model and serum of patients with age-related macular degeneration.BMC biology · 2025Article
- iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.Stem cells translational medicine · 2025Review
- Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.Developmental cell · 2024Article
- Characterization of drusen formation in a primary porcine tissue culture model of dry AMD.Molecular therapy. Methods & clinical development · 2024Article
- The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium.Free radical biology & medicine · 2024Article
- Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.Investigative ophthalmology & visual science · 2024Article
- Article
- iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.Investigative ophthalmology & visual science · 2024Article
- CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
- The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration.Molecular biology reports · 2024Article
- Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.Regenerative biomaterials · 2024Article
- Review: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.Molecular vision · 2024Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich "drusen-like" composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE-ECM interface.
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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.