ArticleMolecular vision2012
Quiescent keratocytes fail to repair MMC induced DNA damage leading to the long-term inhibition of myofibroblast differentiation and wound healing.
Article in Molecular vision, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Potential therapeutic effects of peroxisome proliferator-activated receptors on corneal diseases.Experimental biology and medicine (Maywood, N.J.) · 2024Review
- Molecular and Cellular Mechanisms of Corneal Scarring and Advances in Therapy.International journal of molecular sciences · 2023Article
- Antifibrotic Effects of Caffeine, Curcumin and Pirfenidone in Primary Human Keratocytes.International journal of molecular sciences · 2023Article
- Corneal Endothelial Cell Loss in Glaucoma and Glaucoma Surgery and the Utility of Management with Descemet Membrane Endothelial Keratoplasty (DMEK).Journal of ophthalmology · 2022Review
- Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes.Scientific reports · 2021Article
- Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells.Scientific reports · 2021Article
- Corneal stromal mesenchymal stem cells: reconstructing a bioactive cornea and repairing the corneal limbus and stromal microenvironment.International journal of ophthalmology · 2021Review
- USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea.Molecular therapy. Nucleic acids · 2020Article
- Transient Mitomycin C-treatment of human corneal epithelial cells and fibroblasts alters cell migration, cytokine secretion, and matrix accumulation.Scientific reports · 2019Article
- Impact of topical anti-fibrotics on corneal nerve regeneration in vivo.Experimental eye research · 2019Article
- Molecular basis of Mitomycin C enhanced corneal sensory nerve repair after debridement wounding.Scientific reports · 2018Article
- Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo.Investigative ophthalmology & visual science · 2018Article
- Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea.Experimental eye research · 2017Article
- ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis.Scientific reports · 2016Article
- Reversal of fibrosis by TGF-β3 in a 3D in vitro model.Experimental eye research · 2014Article
- Inhibitory effects of PPARγ ligands on TGF-β1-induced corneal myofibroblast transformation.The American journal of pathology · 2014Article
- TGFβ and PDGF-B signaling blockade inhibits myofibroblast development from both bone marrow-derived and keratocyte-derived precursor cells in vivo.Experimental eye research · 2014Article
- Epithelial cells as alternative human biomatrices for comet assay.Frontiers in genetics · 2014Review
- The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy.PPAR research · 2014Article
- Mouse strain variation in SMA(+) myofibroblast development after corneal injury.Experimental eye research · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe purpose of this study was to determine the acute and long-term effects of mitomycin C (MMC) on quiescent rabbit corneal keratocytes regarding cell proliferation, myofibroblast differentiation and DNA repair.
methodsQuiescent keratocytes cultured in serum-free media were exposed to various concentrations of MMC and then treated with transforming growth factor-β (TGFβ). DNA damage was evaluated in both cultured keratocytes and live rabbit eyes following treatment with MMC. The long-term ability of quiescent keratocytes to repair MMC induced damage in vivo was evaluated in rabbits treated with MMC 2 months before 100 μm deep lamellar keratectomy (LK) injury.
resultsMMC significantly blocked TGFβ-induced cell proliferation and myofibroblast differentiation in cultured quiescent keratocytes and altered the transcriptional regulation of macrophage chemotactic protein-1 (MCP-1) and alpha smooth muscle actin (αSMA). MMC also induced phosphorylation of the nuclear histone marker of DNA damage, γH2AX (a member of the H2A histone family), without induction of cell cycle entry or immediate DNA repair measured by Comet assay. In live rabbits, 0.2 mg/ml MMC significantly induced γH2AX nuclear immunostaining (p<0.05) throughout the cornea and corneas receiving 0.2 mg/ml MMC treatment 2 months before LK injury showed complete absence of any corneal scarring.
conclusionsMMC induces DNA damage to quiescent corneal keratocytes, which remains unrepaired, resulting in abnormal cell replication and gene transcription that leads to long-term effects on corneal repair. Overall these findings suggest that there may be long-term and perhaps permanent consequences to the application of MMC as an anti-fibrotic therapy.
Indexed as
Identifiers
22815636PMC3398499W2159081023What OpenQuestion holds
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.