The chronic stress risk phenotype mirrored in the human retina as a neurodegenerative condition

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Leoné Malan - (Author)
  • Roelof van Wyk - (Author)
  • Roland von Känel - (Author)
  • Tjalf Ziemssen - , Department of Neurology (Author)
  • Walthard Vilser - (Author)
  • Peter M. Nilsson - (Author)
  • Martin Magnusson - (Author)
  • Amra Jujic - (Author)
  • Daniel W. Mak - (Author)
  • Faans Steyn - (Author)
  • Nico T. Malan - (Author)

Abstract

The brain is the key organ that orchestrates the stress response which translates to the retina. The retina is an extension of the brain and retinal symptoms in subjects with neurodegenerative diseases substantiated the eye as a window to the brain. The retina is used in this study to determine whether chronic stress reflects neurodegenerative signs indicative of neurodegenerative conditions. A three-year prospective cohort (n = 333; aged 46 ± 9 years) was stratified into stress-phenotype cases (n = 212) and controls (n = 121) by applying the Malan stress-phenotype index. Neurodegenerative risk markers included ischemia (astrocytic S100 calcium-binding protein B/S100B); 24-h blood pressure, proteomics; inflammation (tumor-necrosis-factor-α/TNF-α); neuronal damage (neuron-specific-enolase); anti-apoptosis of retinal-ganglion-cells (beta-nerve-growth-factor), astrocytic activity (glial-fibrillary-acidic-protein); hematocrit (viscosity) and retinal follow-up data [vessels; stress-optic-neuropathy]. Stress-optic-neuropathy risk was calculated from two indices: a newly derived diastolic-ocular-perfusion-pressure cut-point ≥68 mmHg relating to the stress-phenotype; combined with an established cup-to-disk ratio cut-point ≥0.3. Higher stress-optic-neuropathy (39% vs. 17%) and hypertension (73% vs. 16%) prevalence was observed in the stress-phenotype cases vs. controls. Elevated diastolic-ocular-perfusion-pressure, indicating hypoperfusion, was related to arterial narrowing and trend for ischemia increases in the stress-phenotype. Ischemia in the stress-phenotype at baseline, follow-up and three-year changes was related to consistent inflammation (TNF-α and cytokine-interleukin-17-receptor-A), neuron-specific-enolase increases, consistent apoptosis (chitinase-3-like protein 1, low beta-nerve-growth-factor), glial-fibrillary-acidic-protein decreases, elevated viscosity, vein widening as risk marker of endothelial dysfunction in the blood-retinal barrier, lower vein count, and elevated stress-optic-neuropathy. The stress-phenotype and related neurodegenerative signs of ongoing brain ischemia, apoptosis and endothelial dysfunction compromised blood–retinal barrier permeability and optic nerve integrity. In fact, the stress-phenotype could identify persons at high risk of neurodegeneration to indicate a neurodegenerative condition.

Details

Original languageEnglish
Article number2210687
JournalStress
Volume26
Issue number1
Publication statusPublished - 2 Jan 2023
Peer-reviewedYes

External IDs

Scopus 85160968489
Mendeley e86c5a3d-c607-3e59-a5d5-46d597b27a44

Keywords

Keywords

  • Chronic stress-phenotype, S100B, blood–retinal barrier, neurodegeneration, optic-neuropathy, proteomics, ß-NGF