Evidence map›Paper›PMID 39299675›Full record

ArticleExperimental eye research2024

Corneal epithelial-stromal constructs to study differences associated with diabetes mellitus.

Brenna S Hefley, Tina B McKay, Audrey E K Hutcheon, Joseph B Ciolino, Dimitrios Karamichos

Abstract read
In one paragraph

Article in Experimental eye research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Characterizing Extracellular Vesicles from Biological Fluids.Journal of visualized experiments : JoVE · 2025
    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

5 authors.

Brenna S HefleyNorth Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA; Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.
Tina B McKayDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Audrey E K HutcheonDepartment of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
Joseph B CiolinoDepartment of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
Dimitrios KaramichosNorth Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA; Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. Electronic address: Dimitrios.karamichos@unthsc.edu.

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
Research Resource for Human Organs and Tissues (U42)U42OD011158 · OD · NATIONAL DISEASE RESEARCH INTERCHANGE · PI BELL, THOMAS J · 2012 to 2025
$25.0M
CORNEAL STROMAL-EPITHELIAL INTERACTIONS DURING REPAIRR01EY005665 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Joseph B. Ciolino · 1985 to 2026
$14.4M
Training Program in the Molecular Bases of Eye DiseasesT32EY007145 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore, MEREDITH GREGORY-KSANDER · 1997 to 2026
$4.5M
A Novel Pathogenic Pathway for Diabetic KeratopathyR01EY028949 · NEI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Dimitrios Karamichos, Jian-Xing Jay Ma · 2018 to 2026
$2.2M
Sex Hormones and KeratoconusR01EY028888 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI KARAMICHOS, DIMITRIOS · 2018 to 2020
$1.1M
NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY005665NEI NIH HHS R01 EY028888NEI NIH HHS R01 EY028949NEI NIH HHS T32 EY007145NIH HHS U42 OD011158
6 · The paper itself

Abstract

Diabetes mellitus (DM) is a common metabolic disease associated with severe macrovascular and microvascular complications that influence nearly every tissue in the body, including the anterior and posterior segments of the eye. In the cornea, DM is associated with recurrent epithelial erosion and reduced wound-healing capacity, which increases the risk of corneal scarring. We previously developed a co-culture model of the cornea consisting of immortalized human corneal epithelial cells (hCE-TJ) overlaying a self-assembled stromal layer generated by human corneal fibroblasts (hCFs) over a 4-week period. In this study, we investigated epithelial-stromal constructs generated from hCFs derived from subjects with Type 1 (T1DM) or 2 diabetes (T2DM) compared to controls. We found that T2DM constructs exhibited a disrupted epithelium and a thicker, stratified stromal layer compared to controls or T1DM. Both T1DM and T2DM stromal constructs expressed lower expression of thrombospondin-1 in isolated extracellular vesicles (EVs) compared to controls with no significant difference observed in the presence of epithelial cells, suggesting that reduced provisional matrix secretion in the corneal stroma may be a factor that promotes delayed corneal wound healing in diabetes. The tetraspanins are established extracellular vesicle (EV) markers and include CD63, CD81, and CD9, and were highly expressed by EVs in all three cell types. Control corneal stromal fibroblasts produced more and larger EVs when compared to T1DM and T2DM hCF-derived EVs, supporting a role for altered cell-cell communication in the context of DM. Further characterization of EVs and their cargo is expected to aid in the development of targeted treatments to improve corneal wound healing.

Indexed as

Coculture TechniquesCorneal StromaDiabetes Mellitus, Type 2Epithelium, CornealCells, CulturedDiabetes Mellitus, Type 1FibroblastsHumansMaleThrombospondin 1Wound HealingThrombospondin 1Diabetic neuropathyEndosomalExosomesExtracellular vesiclesKeratectomyTissue-engineered cornea

Identifiers

PMID39299675
PMCPMC12425562

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.