Evidence map›Paper›PMID 39998459›Full record

ArticleInvestigative ophthalmology & visual science2025

Identification of Wnt-5a Receptors Important in Diabetic and Non-Diabetic Corneal Epithelial Wound Healing.

Ruchi Shah, Cynthia Amador, Adam J Poe, Tanya M Spektor, Priyanka Bhandary, Yizhou Wang, Zhiping Paul Wang, Daniel J Weisenberger, Vanessa F Borges, Onkar B Sawant and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
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

15 authors.

Ruchi ShahBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Cynthia AmadorBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Adam J PoeBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Tanya M SpektorBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Priyanka BhandaryDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Yizhou WangDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Zhiping Paul WangDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Daniel J WeisenbergerKeck School of Medicine, University of Southern California, Los Angeles, California, United Sates.
Vanessa F BorgesBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Onkar B SawantCenter for Vision and Eye Banking Research, Eversight, Cleveland, Ohio, United States.
Ezra MaguenAmerican Eye Institute, Los Angeles, California, United States.
Pedram HamrahCornea Service, New England Eye Center, Tufts Medical Center, Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States.
Andrei A KramerovBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Mehrnoosh SaghizadehBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.
Alexander V LjubimovBiomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United Sates.

Funding

Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · CEDARS-SINAI MEDICAL CENTER · 2001 to 2025
$2.0M
The Role of MicroRNAs in Normal and Diseased Corneal Epithelial HomeostasisR01EY025377 · CEDARS-SINAI MEDICAL CENTER · 2025 to 2025
$472k
NEI NIH HHS R01 EY013431NEI NIH HHS R01 EY025377NEI NIH HHS R01 EY029829NEI NIH HHS R01 EY031377
6 · The paper itself

Abstract

Purpose: Persistent epithelial alterations such as delayed wound healing are a key feature of diabetic corneal disease. Previously, we reported that epigenetic changes in the diabetic cornea led to the suppression of Wnt-5a, and that addition of Wnt-5a accelerated wound healing. In this study, we set to determine which Wnt receptor(s) mediated Wnt-5a induced stimulation of diabetic corneal epithelial wound healing. Methods: Human limbal epithelial cells (LECs) were isolated from postmortem diabetic and non-diabetic donor eyes for single-cell RNA sequencing (scRNA-seq) and DNA methylation analysis. These analyses were validated by qRT-PCR, western blot, or immunostaining of corneal tissue sections. Cultured primary LECs were transfected with small interfering RNA (siRNA) to specific Wnt receptors to evaluate their role in scratch wound healing in the presence or absence of 200 ng/mL Wnt-5a. Results: Single-cell RNA sequencing analysis revealed differential gene expression of Wnt receptors, ROR2, MCAM, FZD5, FZD6, and FZD7. DNA methylation arrays showed hypomethylation of ROR2 gene promoter in diabetic versus non-diabetic LECs by 41.3% (**P < 0.01) resulting in increased ROR2 protein expression. Non-diabetic cells transfected with siRNA to knockdown ROR2 but not FZD5, FZD6, FZD7, MCAM, and RYK showed significantly decreased wound healing by approximately 50% (*P < 0.05) versus control siRNA. In diabetic LECs, knockdown of ROR2 significantly inhibited wound healing by 40% (*P < 0.05) and of FZD5 partially blocked wound healing that could not be restored by the addition of Wnt-5a. Conclusions: Wnt-5a seems to mediate wound healing in diabetic LECs mainly through receptor tyrosine kinase like orphan receptor 2 with Frizzled-5 serving as a possible co-receptor with a smaller effect.

Indexed as

Corneal DiseasesEpithelium, CornealGene Expression RegulationReceptors, WntWnt-5a ProteinWound HealingAgedBlotting, WesternCells, CulturedDNA MethylationFemaleFrizzled ReceptorsHumansLimbus CorneaeMaleMiddle AgedFrizzled ReceptorsReceptors, WntReceptor Tyrosine Kinase-like Orphan ReceptorsROR2 protein, humanWnt-5a ProteinWNT5A protein, human

Identifiers

PMID39998459
PMCPMC11875028

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.