ArticleInvestigative ophthalmology & visual science2025
Chronic Restraint Stress Misaligns Corneal Clock via β-Adrenergic and Glucocorticoid Signaling, Altering Epithelial, Neural, Immune, Metabolic States.
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 2 papers.
What it found
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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.
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Who cites it
2 citing papers in PubMed.
- Nocturnal Dim Blue Light Is Associated with Splenic Immune Dysregulation and Altered CORT-GR Signalling in High-Fat-Diet-Fed Mice.Antioxidants (Basel, Switzerland) · 2026Article
- Trihexyphenidyl Ameliorates Depression-like Behaviors in Adult Zebrafish Exposed to Chronic Unpredictable Stress, Consistent with Regulation of the MAPK Signaling Pathway.Biomolecules · 2026Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To determine whether chronic restraint stress (RS), a validated model of chronic psychological stress, disrupts the corneal circadian transcriptome and alters epithelial, neural, immune, and metabolic outputs, and to distinguish the relative contributions of β-adrenergic and glucocorticoid signaling. Methods: Male C57BL/6J mice were subjected to RS for 2 h/day at ZT3 (Zeitgeber Time 3) for 14 consecutive days. Cohorts received either propranolol, metyrapone, or no intervention; non-stressed littermates served as controls. Systemic stress activation was confirmed via plasma levels of adrenocorticotropic hormone, corticosterone, epinephrine, and norepinephrine, along with superior cervical ganglion and adrenal gene expression. Whole corneas were collected every three hours over a 24-hour cycle (ZT0-ZT21) and analyzed by bulk RNA sequencing. Rhythmic transcripts were identified using JTK_CYCLE; differential gene screening was performed using DESeq2. Epithelial mitoses, immune-cell counts, ZO-1/occludin expression, subbasal nerve architecture, and Cochet-Bonnet corneal sensitivity were assessed. Results: RS induced a broad phase advance and amplitude attenuation of rhythmic genes, with downstream reprogramming of immune, proliferative, and metabolic pathways. Phenotypically, RS increased corneal mechanical sensitivity, reduced neutrophil and γδ T-cell counts, elevated epithelial mitotic activity, and diminished ZO-1/occludin expression, whereas subbasal nerve length remained unaffected. Propranolol partially restored circadian phase alignment and improved epithelial and metabolic parameters; metyrapone preferentially enhanced immune-related gene activity and immune-cell abundance. Conclusions: RS disrupts corneal circadian output and impairs epithelial, immune, and metabolic homeostasis via β-adrenergic and glucocorticoid mechanisms. Temporal targeting of these neuroendocrine pathways may represent a strategy to mitigate stress-induced ocular-surface dysfunction.
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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 Socratic graph.