ArticleInvestigative ophthalmology & visual science2020
Altered Protein Function Caused by AMD-associated Variant rs704 Links Vitronectin to Disease Pathology.
Article in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.The Lancet. Rheumatology · 2024Pooled it
- Transcriptomic Profiling of the Human Retina Reveals Inflammatory and Metabolic Signatures Associated With Clinical Severity After Retinal Detachment.Investigative ophthalmology & visual science · 2026Article
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- Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.Experimental eye research · 2025Review
- Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.Investigative ophthalmology & visual science · 2025Article
- Applying low levels of strain to model nascent phenomenon of retinal pathologies.Lab on a chip · 2024Article
- Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification.Nature genetics · 2024Article
- Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development.Nature communications · 2024Article
- Single-Cell RNA Sequencing Reveals Transcriptional Signatures and Cell-Cell Communication in Diabetic Retinopathy.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Therapeutic targets for age-related macular degeneration: proteome-wide Mendelian randomization and colocalization analyses.Frontiers in neurology · 2024Article
- Vitronectin promotes proliferation and metastasis of cervical cancer cells via the epithelial-mesenchymal transition.Frontiers in oncology · 2024Article
- Article
- The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.Frontiers in immunology · 2023Review
- Transient Retention of Photoreceptor Outer Segments in Matrigel-Embedded Retinal Organoids.International journal of molecular sciences · 2022Article
- Role of Vitronectin and Its Receptors in Neuronal Function and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Retinoschisin and novel Na/K-ATPase interaction partners Kv2.1 and Kv8.2 define a growing protein complex at the inner segments of mammalian photoreceptors.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- Complement Mediators in Development to Treat Age-Related Macular Degeneration.Drugs & aging · 2022Review
- Thrombospondin-1 Signaling Through the Calreticulin/LDL Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma.Frontiers in cell and developmental biology · 2022Review
- Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration.Journal of personalized medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Vitronectin, a cell adhesion and spreading factor, is suspected to play a role in the pathogenesis of age-related macular degeneration (AMD), as it is a major component of AMD-specific extracellular deposits (e.g., soft drusen, subretinal drusenoid deposits). The present study addressed the impact of AMD-associated non-synonymous variant rs704 in the vitronectin-encoding gene VTN on vitronectin functionality. Methods: Effects of rs704 on vitronectin expression and processing were analyzed by semi-quantitative sequencing of VTN transcripts from retinal pigment epithelium (RPE) cells generated from human induced pluripotent stem cells (hiPSCs) and from human neural retina, as well as by western blot analyses on heterologously expressed vitronectin isoforms. Binding of vitronectin isoforms to retinal and endothelial cells was analyzed by western blot. Immunofluorescence staining followed extracellular matrix (ECM) deposition in cultured RPE cells heterologously expressing the vitronectin isoforms. Adhesion of fluorescently labeled RPE or endothelial cells in dependence of recombinant vitronectin or vitronectin-containing ECM was investigated fluorometrically or microscopically. Tube formation and migration assays addressed effects of vitronectin on angiogenesis-related processes. Results: Variant rs704 affected expression, secretion, and processing but not oligomerization of vitronectin. Cell binding and influence on RPE-mediated ECM deposition differed between AMD-risk-associated and non-AMD-risk-associated protein isoforms. Finally, vitronectin affected adhesion and endothelial tube formation. Conclusions: The AMD-risk-associated vitronectin isoform exhibits increased expression and altered functionality in cellular processes related to the sub-RPE aspects of AMD pathology. Although further research is required to address the subretinal disease aspects, this initial study supports an involvement of vitronectin in AMD pathogenesis.
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