ArticlePloS one2017
Extracellular matrix nitration alters growth factor release and activates bioactive complement in human retinal pigment epithelial cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Skin Melanin Content and the Foveal Avascular Zone Correlation in a Healthy White Population.Investigative ophthalmology & visual science · 2026Article
- Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025Article
- The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.Frontiers in immunology · 2023Review
- Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2022Article
- AMD-Like Substrate Causes Epithelial Mesenchymal Transition in iPSC-Derived Retinal Pigment Epithelial Cells Wild Type but NotInternational journal of molecular sciences · 2021Article
- Retinal capillary basement membrane thickening: Role in the pathogenesis of diabetic retinopathy.Progress in retinal and eye research · 2021Review
- The complement system in age-related macular degeneration.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy.International journal of molecular sciences · 2021Review
- The Long Pentraxin PTX3 as a New Biomarker and Pharmacological Target in Age-Related Macular Degeneration and Diabetic Retinopathy.Frontiers in pharmacology · 2021Review
- Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions.Stem cells translational medicine · 2020Article
- Retinal pigment epithelium polarity in health and blinding diseases.Current opinion in cell biology · 2020Review
- Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization.Oxidative medicine and cellular longevity · 2020Review
- Oxidative Stress Increases Endogenous Complement-Dependent Inflammatory and Angiogenic Responses in Retinal Pigment Epithelial Cells Independently of Exogenous Complement Sources.Antioxidants (Basel, Switzerland) · 2019Article
- Role ofTaiwan journal of ophthalmologyReview
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeWe have shown previously that non-enzymatic nitration (NEN) of the extracellular matrix (ECM), which serves as a model of Bruch's membrane (BM) aging, has a profound effect on the behavior of the overlying retinal pigment epithelial (RPE) cells, including altered phagocytic ability, reduced cell adhesion, and inhibition of proliferation. We know that transplanted RPE monolayers will encounter a hostile sub-RPE environment, including age-related alterations in BM that may compromise cell function and survival. Here we use our previous NEN model of BM aging to determine the effects of NEN of the ECM on growth factor release and complement activation in RPE cells.
methodsHuman induced-pluripotent stem cells (iPSCs) were differentiated into RPE cells, and confirmed by immunohistochemistry, confocal microscopy, and polymerase chain reaction. IPSC-derived RPE cells were plated onto RPE-derived ECM under untreated or nitrite-modified conditions. Cells were cultured for 7 days and barrier function measured by transepithelial resistance (TER). Vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), and complement component C3a were measured using enzyme-linked immunosorbent assay (ELISA).
resultsOn average nitrite-modified ECM increased VEGF release both apically and basally by 0.15 ± 0.014 ng/mL (p <0.0001) and 0.21 ± 0.022 ng/mL (p <0.0001), respectively, in iPSC-derived RPE cells. Nitrite-modified ECM increased PEDF release in iPSC-derived RPE cells apically by 0.16 ± 0.031 ng/mL (p <0.0001), but not basally (0.27 ± 0.015 vs. 0.32 ± 0.029 ng/mL, (p >0.05)). Nitrite-modified ECM increased production of C3a in iPSC-derived RPE cells by 0.52 ± 0.123 ng/mL (p <0.05).
conclusionNitrite-modified ECM increased VEGF, PEDF release, and C3a production in human iPSC-derived RPE cells. This model demonstrates changes seen in the basement membrane can lead to alterations in the cell biology of the RPE cells that may be related to the development of age-related macular degeneration.
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