Retinal-glia ischemia and inflammation induced by chronic stress: The SABPA study

Leoné Malan; Mark Hamer; Roland von Känel; Roelof D van Wyk; Annemarie Wentzel; Hendrik S Steyn; Pieter van Vuuren; Nico T Malan

doi:10.1016/j.bbih.2019.100027

Retinal-glia ischemia and inflammation induced by chronic stress: The SABPA study

Brain Behav Immun Health. 2019 Dec 17:2:100027. doi: 10.1016/j.bbih.2019.100027. eCollection 2020 Feb.

Authors

Leoné Malan¹, Mark Hamer², Roland von Känel³, Roelof D van Wyk⁴, Annemarie Wentzel¹, Hendrik S Steyn⁵, Pieter van Vuuren⁶, Nico T Malan¹

Affiliations

¹ Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, 2520, South Africa.
² Division Surgery & Interventional Science, University College London, United Kingdom.
³ Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, 8091, Switzerland.
⁴ Surgical Ophthalmologist, 85 Peter Mokaba Street, Potchefstroom, 2531, South Africa.
⁵ Statistical Consultation Services, North-West University, Potchefstroom, 2520, South Africa.
⁶ School of Electrical, Electronic and Computer Engineering, North-West University, Potchefstroom, 2520, South Africa.

Abstract

Background: Psychobiological processes linking stress and vascular diseases remain poorly understood. The retina and the brain share a common embryonic-diencephalon origin and blood-barrier physiology e.g. ongoing ischemia facilitates S100B release with astrocytic activity and glial-fibrillary-acidic-protein expression (GFAP). However, GFAP decreases revealed astrocyte pathology in the prefrontal cortex of depression/suicide cases; and might be a key mechanism in stress - disease pathways.

Methods: A chronic emotional stress phenotype independent of age, ethnicity or sex was used to stratify the current prospective cohort (N = 359; aged 46 ± 9 years) into Stress (N = 236) and no-Stress groups (N = 123). Prospective data for glia ischemia risk markers were obtained, including 24 h BP, fasting S100B, GFAP, HbA_1C and tumor-necrosis-factor-α (TNF-α). At 3-yr follow-up: diastolic-ocular-perfusion-pressure (indicating hypo-perfusion risk) was measured and retinal vessel calibers were quantified from digital images in the mydriatic eye.

Results: Higher hypertension (75% vs. 16%), diabetes (13% vs. 0%) and retinopathy (57% vs. 45%) prevalence was observed in Stress compared to no-Stress individuals. Stressed individuals had consistently raised S100B, TNF-α, HbA_1C and higher diastolic-ocular-perfusion-pressure, but decreases in GFAP and GFAP:S100B. Furthermore stroke risk markers, arterial narrowing and venous widening were associated with consistently raised S100B, GFAP:S100B (p = 0.060), TNF-α and higher diastolic-ocular-perfusion-pressure [Adj. R² 0.39-0.41, p ≤ 0.05]. No retinal-glia associations were evident in the no-Stress group.

Conclusions: Retinal-glia ischemia and inflammation was induced by chronic stress. Persistent higher inflammation and S100B with GFAP decreases further reflected stress-induced astrocyte pathology in the human retina. It is recommended to increase awareness on chronic stress and susceptibility for brain ischemia.

Keywords: Glia; Inflammation; Ischemia; Retina; Stress.