ArticleInvestigative ophthalmology & visual science2012
Endothelial Cdkn1a (p21) overexpression and accelerated senescence in a mouse model of Fuchs endothelial corneal dystrophy.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Sex-Specific Differences in Corneal Remodeling after Descemet Membrane Endothelial Keratoplasty in Fuchs Endothelial Corneal Dystrophy.Ophthalmology science · 2026Article
- Cross-Cohort Evidence of Editome Dysregulation and Cell Growth-Related IGFBP7 Recoding Driven by ADARB1 in Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate NADPH-Driven Oxidative Stress.Biomolecules & therapeutics · 2026Article
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Single-Short Partial Reprogramming of the Endothelial Cells Decreases Blood Pressure via Attenuation of EndMT in Hypertensive Mice.Circulation research · 2025Article
- Review
- METTL3-mCell death discovery · 2025Article
- MitoQ relieves mitochondrial dysfunction in UVA and cigarette smoke-induced Fuchs endothelial corneal dystrophy.Experimental eye research · 2024Article
- The influence of obesity, diabetes mellitus and smoking on fuchs endothelial corneal dystrophy (FECD).Scientific reports · 2024Article
- Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.Aging · 2024Article
- An interferon gamma response signature links myocardial aging and immunosenescence.Cardiovascular research · 2023Article
- Cellular senescence and ophthalmic diseases: narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Review
- A single-cell RNA-seq analysis unravels the heterogeneity of primary cultured human corneal endothelial cells.Scientific reports · 2023Article
- Single cell RNA-seq of human cornea organoids identifies cell fates of a developing immature cornea.PNAS nexus · 2022Article
- Identification of novel therapeutic targets for Fuchs' endothelial corneal dystrophy based on gene bioinformatics analysis.PloS one · 2022Article
- Review
- Start codon disruption with CRISPR/Cas9 prevents murine Fuchs' endothelial corneal dystrophy.eLife · 2021Article
- Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System.International journal of molecular sciences · 2021Review
- Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy.Free radical biology & medicine · 2021Article
- Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis.Progress in retinal and eye research · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeStress of the endoplasmic reticulum and oxidative stress play critical roles in the pathogenesis of Fuchs Endothelial Corneal Dystrophy (FECD). In the normal aging cornea, cellular stress has been associated with a loss in proliferative capacity (premature senescence) of corneal endothelial cells (CECs). The present study used a transgenic Col8a2(Q455K/Q455K) knock-in mouse model of early-onset FECD to identify the endothelial expression profile of specific cellular stress response-related targets, which may be relevant to late-onset FECD.
methodsThe differential endothelial mRNA levels of cellular stress response-related genes were determined in 12-month-old homozygous Col8a2(Q455K/Q455K) mutant and wild-type mice using customized PCR arrays. Result validation and analysis of additional senescence-related transcripts was performed by real-time PCR. Expression of p53 and p21 was assessed by immunofluorescence. Senescence-associated β-galactosidase (SA-β-Gal) activity was investigated by histochemical labeling. Human FECD samples and normal controls were examined for p21 expression by immunohistochemistry.
resultsPCR-array analysis showed greater than 2-fold and/or significantly altered endothelial regulation of 19 cellular stress response-related transcripts in Col8a2(Q455K/Q455K) mutant mice; real-time PCR documented statistically significant upregulation of senescence-associated targets Cdkn1a (p21), Serpine1 (PAI-1), Tagln (Sm22), Fn1 and Clu (ApoJ). Immunofluorescence revealed increased expression of nuclear p53 and p21 in mutant animals. SA-β-Gal staining detected increased proportions of senescent CECs in mutant mice. Human FECD endothelium exhibited increased levels of nuclear p21 protein.
conclusionsOur results identify endothelial Cdkn1a (p21) upregulation in a mouse model of early-onset FECD, confirm overexpression of p21 in late-onset human FECD endothelium, and suggest a role for premature senescence in FECD.
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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.