Retinal-glia ischemia and inflammation induced by chronic stress: The SABPA study
Retinal-glia ischemia and inflammation induced by chronic stress: The SABPA study
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DOI：
10.1016/j.bbih.2019.100027
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发表时间：
2019-12-17
期刊：
影响因子：
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通讯作者：
Malan NT
中科院分区：
文献类型：
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作者：
Malan L;Hamer M;von Känel R;van Wyk RD;Wentzel A;Steyn HS;van Vuuren P;Malan NT
人们对压力和血管疾病之间的心理生物学过程仍然知之甚少。视网膜和脑共享共同的胚胎间脑起源和血液屏障生理学，例如持续的缺血促进具有星形胶质细胞活性和胶质细胞酸性蛋白表达（GFAP）的S100 B释放。然而，GFAP减少揭示了抑郁症/自杀病例的前额叶皮层中的星形胶质细胞病理学;并且可能是应激-疾病途径中的关键机制。使用与年龄、种族或性别无关的慢性情绪应激表型将当前前瞻性队列（N = 359;年龄46 ± 9岁）分层为应激组（N = 236）和无应激组（N = 123）。获得胶质缺血风险标志物的前瞻性数据，包括24 h BP、空腹S100 B、GFAP、HbA 1C和肿瘤坏死因子-α（TNF-α）。3年随访时：测量瞳孔-眼-灌注-压（指示低灌注风险），并且从散瞳眼中的数字图像定量视网膜血管口径。高血压（75%对16%），糖尿病（13%对0%）和视网膜病变（57%对45%）的患病率在压力下观察到与无压力的人相比。应激个体的S100 B、TNF-α、HbA 1C和眼动脉灌注压持续升高，而GFAP和GFAP：S100 B降低。此外，卒中风险标志物、动脉狭窄和静脉增宽与持续升高的S100 B、GFAP：S100 B（p = 0.060）、TNF-α和较高的眼动脉灌注压相关[R2 0.39-0.41，p ≤ 0.05]。在无压力组中没有明显的视网膜-神经胶质关联。慢性应激诱导视网膜神经胶质细胞缺血和炎症。持续较高的炎症和S100 B与GFAP降低进一步反映了人类视网膜中应激诱导的星形胶质细胞病理学。建议提高对慢性应激和脑缺血易感性的认识。高血压、视网膜病变和灌注缺陷在慢性应激个体中增强。应激诱导的缺血促进了S100 B和TNF-α的持续释放，但GFAP减少。视网膜动脉变窄和静脉增宽反映了缺血和内皮功能障碍。应激诱导的星形胶质细胞缺血病理在人视网膜中是明显的。建议提高对慢性应激和脑缺血易感性的认识。
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. 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, HbA1C 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. 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, HbA1C 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. 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. Hypertension, retinopathy and perfusion deficits are enhanced in chronic stressed individuals. Stress-induced ischemia facilitated consistent S100B and TNF-α release but GFAP decreases. Retinal arterial narrowing and venous widening reflected ischemia and endothelial dysfunction. Stress-induced astrocyte ischemia pathology was evident in the human retina. It is recommended to increase awareness on chronic stress and susceptibility for brain ischemia.