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

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. R 2 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.

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

“…The Stressed group showed higher prevalence of smoking and greater alcohol consumption as well as more dementia and retinal vascular dysregulation risk signs compared to the non-Stressed group ( p < 0.05). Compared to their counterparts, the Stressed group also presented higher diabetes-prone symptoms (higher prevalence of ethnicity-specific central obesity, dyslipidemia, low-grade inflammation, lower cognitive exe-func control scores, lower IGF-1 and IGFBP-3 levels, higher glycated hemoglobin and insulin, increased prevalence of hyperinsulinemia, triglyceridemia, pre-diabetes, diabetes, HOMA-IR, hypertension (74%) as well as increased retinopathy prevalence (62%), fewer retinal arteries, increased arterial narrowing, vein widening and AV nicking (74%) and higher perfusion deficit levels (glia ischemia (S100B) and higher diastolic ocular perfusion pressure) as risk markers of stroke [ 14 ].…”

“…The following dementia-related risk markers indicating cardiometabolic perturbations [ 1 , 2 , 3 , 4 , 5 , 6 ], neurodegeneration [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ] and vascular dysregulation [ 14 , 15 , 27 ] were specified and included in the current investigation (in no particular order): poorer cognitive executive functioning control [ 30 ]; neuronal glia injury (increased S100B and NSE) [ 19 ]; increased central obesity or waist circumference (WC) [ 32 ]; endothelial dysfuntion (increased von Willebrand factor (VWF)) [ 33 ]; depressed time domain heart rate variability (HRV) ( Supplementary Methodology ) [ 34 ]; increased insulin resistance/HOMA-IR [ 8 ] and inflammation (C-reactive protein/CRP) [ 35 ]; and shorter telomeres [ 21 ].…”

“…Statistica version 13.3 (TIBCO Software Inc., Palo Alto, Santa Clara, CA, USA, 2018) was used for data analyses. We proceeded from previous investigations in the SABPA study [ 14 , 15 ] by applying a validated chronic stress and stroke risk phenotype (hereafter Stressed) score, independent of age, race or gender (see Section 6 ). Participants were stratified into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups.…”

“…Stroke risk markers, i.e., retinal arterial narrowing and vein widening, might further explain a link between T3D and retinopathy or neurodegeneration [ 7 , 13 ]. Therefore, assessment of peripheral biochemical markers indicative of neuronal glia injury can complement neuropsychiatric and diabetic retinopathy evaluation [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Neuron-specific enolase (NSE) [ 16 ] and cytosolic calcium-binding protein, S100B [ 17 ], have been associated with preclinical diabetes diagnosis and prognosis of optic nerve diseases [ 16 , 17 , 18 ]; as well as S100B-related ischemic conditions in the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) cohort [ 14 ].…”

“…It is, then, also to be expected that insulin will affect psychiatric functioning, as it was among the earliest drug treatments for psychiatric disorders [ 24 ]. Determining stress-related T3D risk markers is critically needed, as similar retinal neurovascular dysregulation response patterns have been observed in individuals with chronic stress from the SABPA study [ 14 , 15 ] and in Alzheimer’s dementia individuals [ 25 ].…”