ArticleInvestigative ophthalmology & visual science2013
Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon MMP-10 and cathepsin F gene silencing.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A systematic review on the impact of diabetes mellitus on the ocular surface.Nutrition & diabetes · 2017Pooled it
- Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis.Diabetologia · 2026Article
- Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell.BMC ophthalmology · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Review
- Corneal Epithelial Changes in Diabetic Patients: A Review.International journal of molecular sciences · 2024Review
- Review
- Corneal gene therapy: Structural and mechanistic understanding.The ocular surface · 2023Article
- Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice.Investigative ophthalmology & visual science · 2023Article
- Targeting matrix metalloproteases in diabetic wound healing.Frontiers in immunology · 2023Review
- The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas.Progress in retinal and eye research · 2022Review
- The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates.Cell death & disease · 2022Review
- Gene Therapy in the Anterior Eye Segment.Current gene therapy · 2022Review
- Molecular characteristics and spatial distribution of adult human corneal cell subtypes.Scientific reports · 2021Article
- 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
- Review
- An Update on Corneal Biomechanics and Architecture in Diabetes.Journal of ophthalmology · 2019Review
- Corneal alteration and pathogenesis in diabetes mellitus.International journal of ophthalmology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDiabetic corneas overexpress proteinases including matrix metalloproteinase-10 (M10) and cathepsin F (CF). Our purpose was to assess if silencing M10 and CF in organ-cultured diabetic corneas using recombinant adenovirus (rAV)-driven small hairpin RNA (rAV-sh) would normalize slow wound healing, and diabetic and stem cell marker expression.
methodsSixteen pairs of organ-cultured autopsy human diabetic corneas (four per group) were treated with rAV-sh. Proteinase genes were silenced either separately, together, or both, in combination (Combo) with rAV-driven c-met gene overexpression. Fellow control corneas received rAV-EGFP. Quantitative RT-PCR confirmed small hairpin RNA (shRNA) silencing effect. Ten days after transfection, 5-mm epithelial wounds were made with n-heptanol and healing time recorded. Diabetic, signaling, and putative stem cell markers were studied by immunofluorescence of corneal cryostat sections.
resultsProteinase silencing reduced epithelial wound healing time versus rAV-enhanced green fluorescent protein (EGFP) control (23% for rAV-shM10, 31% for rAV-shCF, and 36% for rAV-shM10 + rAV-shCF). Combo treatment was even more efficient (55% reduction). Staining patterns of diabetic markers (α₃β₁ integrin and nidogen-1), and of activated epidermal growth factor receptor and its signaling target activated Akt were normalized upon rAV-sh treatment. Combo treatment also restored normal staining for activated p38. All treatments, especially the combined ones, increased diabetes-altered staining for putative limbal stem cell markers, ΔNp63α, ABCG2, keratins 15 and 17, and laminin γ3 chain.
conclusionsSmall hairpin RNA silencing of proteinases overexpressed in diabetic corneas enhanced corneal epithelial and stem cell marker staining and accelerated wound healing. Combined therapy with c-met overexpression was even more efficient. Specific corneal gene therapy has a potential for treating diabetic keratopathy.
Indexed as
Identifiers
What 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.