Evidence map›Paper›PMID 21866211›Full record

ArticleMolecular vision2011

Alterations of epithelial stem cell marker patterns in human diabetic corneas and effects of c-met gene therapy.

Mehrnoosh Saghizadeh, Siavash Soleymani, Angel Harounian, Bhavik Bhakta, Sergey M Troyanovsky, William J Brunken, Graziella Pellegrini, Alexander V Ljubimov

Open access · greenAbstract read
In one paragraph

Article in Molecular vision, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.4field-weighted citation impact, top 9% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  3. Article
  4. Article
  5. Corneal Epithelial Changes in Diabetic Patients: A Review.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Review
  8. Article
  9. Elevated Opioid Growth Factor Alters the Limbus in Type 1 Diabetic Rats.Journal of diabetes and clinical research · 2023
    Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Systemic diseases and the cornea.Experimental eye research · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Mehrnoosh SaghizadehOphthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Siavash Soleymani
Angel Harounian
Bhavik Bhakta
Sergey M Troyanovsky
William J Brunken
Graziella Pellegrini
Alexander V Ljubimov
Cedars-Sinai Medical Center · US

Funding

ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2M
Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Alexander V Ljubimov · 2001 to 2026
$11.3M
Inter-junctional signaling in epithelial junctional complexR01AR044016 · NIAMS · WASHINGTON UNIVERSITY · PI TROYANOVSKY, SERGEY M · 1996 to 2020
$6.8M
NCRR NIH HHS M01 RR000425NCRR NIH HHS M01 RR00425NEI NIH HHS R01 EY013431NEI NIH HHS R01 EY13431
6 · The paper itself

Abstract

purposeWe have previously identified specific epithelial proteins with altered expression in human diabetic central corneas. Decreased hepatocyte growth factor receptor (c-met) and increased proteinases were functionally implicated in the changes of these proteins in diabetes. The present study examined whether limbal stem cell marker patterns were altered in diabetic corneas and whether c-met gene overexpression could normalize these patterns.

methodsCryostat sections of 28 ex vivo and 26 organ-cultured autopsy human normal and diabetic corneas were examined by immunohistochemistry using antibodies to putative limbal stem cell markers including ATP-binding cassette sub-family G member 2 (ABCG2), N-cadherin, ΔNp63α, tenascin-C, laminin γ3 chain, keratins (K) K15, K17, K19, β(1) integrin, vimentin, frizzled 7, and fibronectin. Organ-cultured diabetic corneas were studied upon transduction with adenovirus harboring c-met gene.

resultsImmunostaining for ABCG2, N-cadherin, ΔNp63α, K15, K17, K19, and β(1) integrin, was significantly decreased in the stem cell-harboring diabetic limbal basal epithelium either by intensity or the number of positive cells. Basement membrane components, laminin γ3 chain, and fibronectin (but not tenascin-C) also showed a significant reduction in the ex vivo diabetic limbus. c-Met gene transduction, which normalizes diabetic marker expression and epithelial wound healing, was accompanied by increased limbal epithelial staining for K17, K19, ΔNp63α, and a diabetic marker α(3)β(1) integrin, compared to vector-transduced corneas.

conclusionsThe data suggest that limbal stem cell compartment is altered in long-term diabetes. Gene therapy, such as with c-met overexpression, could be able to restore normal function to diabetic corneal epithelial stem cells.

Indexed as

Diabetes MellitusGene ExpressionProto-Oncogene Proteins c-metAdenoviridaeAdolescentAgedAged, 80 and overAutopsyBasement MembraneBiomarkersCells, CulturedChildEpithelium, CornealEye ProteinsFemaleGene Expression ProfilingBiomarkersEye ProteinsMET protein, humanProto-Oncogene Proteins c-met

Identifiers

PMID21866211
PMCPMC3159681
OpenAlexW1513401223

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Registered trials

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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.