ArticleExperimental eye research2014
Normalization of wound healing and stem cell marker patterns in organ-cultured human diabetic corneas by gene therapy of limbal cells.
Article in Experimental eye research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- A systematic review on the impact of diabetes mellitus on the ocular surface.Nutrition & diabetes · 2017Pooled it
- Role of Programmed Cell Death Pathways in Mediating Epithelial Wound Healing and Its Defects in Diabetic Corneas.Investigative ophthalmology & visual science · 2026Article
- Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis.Diabetologia · 2026Article
- Review
- Corneal gene therapy: Structural and mechanistic understanding.The ocular surface · 2023Article
- The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas.Progress in retinal and eye research · 2022Review
- Gene Therapy in the Anterior Eye Segment.Current gene therapy · 2022Review
- Diabetic Corneal Neuropathy: Pathogenic Mechanisms and Therapeutic Strategies.Frontiers in pharmacology · 2022Review
- Article
- Systemic diseases and the cornea.Experimental eye research · 2021Review
- Novel nanopolymer RNA therapeutics normalize human diabetic corneal wound healing and epithelial stem cells.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- Diabetic Corneal Neuropathy.Journal of clinical medicine · 2020Review
- An Update on Corneal Biomechanics and Architecture in Diabetes.Journal of ophthalmology · 2019Review
- Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration, proliferation and marker expression of limbal epithelial cells.Scientific reports · 2018Article
- Limbal stem cells: identity, developmental origin, and therapeutic potential.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Diabetic corneal neuropathy: clinical perspectives.Clinical ophthalmology (Auckland, N.Z.) · 2018Review
- Diabetic complications in the cornea.Vision research · 2017Review
- Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.Scientific reports · 2017Article
- Adenoviral Gene Therapy for Diabetic Keratopathy: Effects on Wound Healing and Stem Cell Marker Expression in Human Organ-cultured Corneas and Limbal Epithelial Cells.Journal of visualized experiments : JoVE · 2016Article
- Stem cell therapies in the treatment of diabetic retinopathy and keratopathy.Experimental biology and medicine (Maywood, N.J.) · 2016Review
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 3 institutions in 1 country.
Funding
Abstract
Overexpression of c-met and suppression of matrix metalloproteinase-10 (MMP-10) and cathepsin F genes was previously shown to normalize wound healing, epithelial and stem cell marker patterns in organ-cultured human diabetic corneas. We now examined if gene therapy of limbal cells only would produce similar effects. Eight pairs of organ-cultured autopsy human diabetic corneas were used. One cornea of each pair was treated for 48 h with adenoviruses (Ad) harboring full-length c-met mRNA or a mixture (combo) of Ad with c-met and shRNA to MMP-10 and cathepsin F genes. Medium was kept at the limbal level to avoid transduction of central corneal epithelium. Fellow corneas received control Ad with EGFP gene. After additional 5 (c-met) or 10 days (combo) incubation, central corneal epithelial debridement with n-heptanol was performed, and wound healing times were determined microscopically. Corneal cryostat sections were immunostained for diabetic and putative limbal stem cell markers, α3β1 integrin, nidogen-1, fibronectin, laminin γ3 chain, ΔNp63α, keratins 14, 15, and 17, as well as for activated signaling intermediates, phosphorylated EGFR, Akt, and p38. Limbal c-met overexpression significantly accelerated healing of 8.5-mm epithelial wounds over EGFP controls (6.3 days vs. 9.5 days, p < 0.02). Combo treatment produced a similar result (6.75 days vs. 13.5 days, p < 0.03). Increased immunostaining vs. EGFP controls for most markers and signaling intermediates accompanied c-met gene or combo transduction. Gene therapy of limbal epithelial stem cell compartment has a beneficial effect on the diabetic corneal wound healing and on diabetic and stem cell marker expression, and shows potential for alleviating symptoms of diabetic keratopathy.
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Registered trials
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