Evidence map›Paper›PMID 40139640›Full record

ArticleExperimental eye research2025

Chronic intermittent hypoxia modulates corneal fibrotic markers and inflammatory cytokine expression in a sex-dependent manner.

Jessica L Bradshaw, Brenda Vasini, Steve Mabry, Brenna S Hefley, E Nicole Wilson, Jennifer J Gardner, Rebecca L Cunningham, Dimitrios Karamichos

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental eye research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

8 authors.

Jessica L BradshawDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Brenda VasiniDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA; North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Steve MabryDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA; North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Brenna S HefleyDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA; North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA.
E Nicole WilsonDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Jennifer J GardnerDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Rebecca L CunninghamDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA. Electronic address: rebecca.cunningham@unthsc.edu.
Dimitrios KaramichosDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA; North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, USA; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA. Electronic address: dimitrios.karamichos@unthsc.edu.

Funding

The Intimate Interplay Between Keratoconus, Sex Hormones, and the Anterior PituitaryR01EY035510 · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2025 to 2025
$394k
NEI NIH HHS R01 EY035510NINDS NIH HHS R01 NS091359
6 · The paper itself

Abstract

Chronic intermittent hypoxia (CIH) is a commonly observed condition in patients suffering from obstructive sleep apnea (OSA). Previous studies link CIH to fibrosis, inflammation, and hormonal dysregulation across various tissues. Yet, the effect of CIH in the cornea is unknown. Moreover, women and men diagnosed with OSA present with diverse symptoms, suggesting sex-specific pathophysiology at play. Thus, we used a rat model to assess the impact of CIH and sex on protein expression of corneal fibrotic markers (α-SMA, COL III, cFN, TSP-1), proinflammatory cytokines (IL-1 α, IL-17, IL-18, and IFN-γ), and hormone receptors (ERα, ERβ, GPER, GnRH-R, and LH-R). Male and female Sprague Dawley rats were exposed to normoxic or CIH conditions during their sleep cycle for 14 days. Extracted corneal proteins were subjected to Western blot and multiplex magnetic bead analysis. Our results reveal sex differences in fibrotic and inflammatory markers in the cornea, whereby female corneas exhibit higher levels of fibrotic markers, while male corneas exhibit increased inflammatory cytokines. CIH exposure resulted in elevated levels of α-SMA and pro-inflammatory cytokines in female corneas, while there was no impact on fibrotic or inflammatory markers in male corneas. Additionally, CIH exposure reduced hormone receptors in male and female corneas in a sex-dependent manner. Correlation analyses identified associations of corneal hormone receptors with corneal fibrotic and pro-inflammatory markers that were dependent on sex, with female corneas demonstrating stronger correlations compared to male corneas. Altogether, our data suggests hormone-mediated signaling may contribute to CIH-mediated corneal fibrosis and inflammatory phenotypes, especially in females.

Indexed as

BiomarkersCorneaCorneal DiseasesCytokinesHypoxiaAnimalsBlotting, WesternChronic DiseaseDisease Models, AnimalFemaleFibrosisMaleRatsRats, Sprague-DawleySex FactorsBiomarkersCytokinesChronic intermittent hypoxiaCorneaFibrosisInflammatory cytokinesSex differencesSex hormone receptors

Identifiers

PMID40139640
PMCPMC12862948

What Socratic 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 Socratic graph.