Role of Neuron–Glia Signaling in Regulation of Retinal Vascular Tone in Rats

Someya, Eriko; Akagawa, Mari; Mori, Akira; Morita, Akane; Yui, Natsuko; Asano, Daiki; Sakamoto, Kenji; Nakahara, Tsutomu

doi:10.3390/ijms20081952

Cited by 9 publications

(16 citation statements)

References 25 publications

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“…Serum TNF-α may translate to brain TNF-α as peripheral TNF-α regulated immune cell trafficking in the mouse brain ( Paouri et al., 2017 ), which support our findings of retinal vein widening and associated serum TNF-α responses, reflecting endothelial dysfunction ( Liew and Wang, 2011 ). Venous widening in the Stress group, was related to inflammatory responsivity and GFAP:S100B decreases, suggestive of GFAP decreases which can reduce activity of GFAP-positive astrocytes ( Someya et al., 2019 ). The stress-induced ongoing ischemia or persistent S100B release will impair myogenic control and increase vascular resistance and -tone (arterial narrowing) ( Liew and Wang, 2011 ; Someya et al., 2019 ) with potential damage to the retinal ganglion cells and optic nerve head.…”

Section: Discussionmentioning

confidence: 99%

“…Venous widening in the Stress group, was related to inflammatory responsivity and GFAP:S100B decreases, suggestive of GFAP decreases which can reduce activity of GFAP-positive astrocytes ( Someya et al., 2019 ). The stress-induced ongoing ischemia or persistent S100B release will impair myogenic control and increase vascular resistance and -tone (arterial narrowing) ( Liew and Wang, 2011 ; Someya et al., 2019 ) with potential damage to the retinal ganglion cells and optic nerve head.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the similar nature of glia cell signaling in the retina and brain suggests similar neuron and glia-blood vessel or neurovascular communication ( Someya et al., 2019 ; Wentzel et al., 2019 ). Ischemic stroke risk increases as both carotid intima media thickening and retinal arterial occlusion risk is apparent ( Piepoli et al., 2016 ; Someya et al., 2019 ; Wentzel et al., 2019 ; Wu et al., 2017 ; Malan et al., 2016b ) in the Stress group (retinal artery narrowing, venous widening and arteriovenous nicking).…”

Section: Discussionmentioning

confidence: 99%

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

Malan

Hamer

Känel

et al. 2020

Brain, Behavior, & Immunity - Health

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Malan

Hamer

Känel

et al. 2020

Brain, Behavior, & Immunity - Health

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“…It remains to be understood to which extent glia-EC signaling is indirectly ( via neurons or pericytes) or directly coupled. Lastly, neuron-derived NO regulates glia-mediated vasodilation via prostanoids and epoxyeicosatrienoic acids ( Someya et al, 2019 ). Together, glial cells therefore not only play a role in angiogenesis, anastomosis, EC maturation, and blood flow regulation, with glia dysfunction potentially leading to BBB breakdown, pathological vascularization, dysregulation of vasoregulation and failure to deliver sufficient oxygenation.…”

Section: Glia Cells and The Neurovascular Unit Vasculature: Angiogenesis And Regulation Of Blood Flowmentioning

confidence: 99%

The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction

Kugler

Greenwood²,

Macdonald³

2021

Front. Cell Dev. Biol.

111

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The neurovascular unit (NVU) is a complex multi-cellular structure consisting of endothelial cells (ECs), neurons, glia, smooth muscle cells (SMCs), and pericytes. Each component is closely linked to each other, establishing a structural and functional unit, regulating central nervous system (CNS) blood flow and energy metabolism as well as forming the blood-brain barrier (BBB) and inner blood-retina barrier (BRB). As the name suggests, the “neuro” and “vascular” components of the NVU are well recognized and neurovascular coupling is the key function of the NVU. However, the NVU consists of multiple cell types and its functionality goes beyond the resulting neurovascular coupling, with cross-component links of signaling, metabolism, and homeostasis. Within the NVU, glia cells have gained increased attention and it is increasingly clear that they fulfill various multi-level functions in the NVU. Glial dysfunctions were shown to precede neuronal and vascular pathologies suggesting central roles for glia in NVU functionality and pathogenesis of disease. In this review, we take a “glio-centric” view on NVU development and function in the retina and brain, how these change in disease, and how advancing experimental techniques will help us address unanswered questions.

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“…Interactions among neuronal, glial, and vascular cells in the retina are critical for the maintenance of an adequate retinal blood flow ( Nakahara et al., 2013 ; Someya et al., 2019 ). We previously reported that the inner nuclear layer of the retina was thinned without retinal ganglion cell loss in diabetic rats ( Mori et al., 2009 ).…”

Section: Discussionmentioning

confidence: 99%

L-Citrulline ameliorates the attenuation of acetylcholine-induced vasodilation of retinal arterioles in diabetic rats

Mori

Takei

Suzuki

et al. 2021

Heliyon

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In our previous study, we found that the vasodilation of retinal arterioles induced by acetylcholine and BMS-191011, a large-conductance Ca 2+ -activated K + (BK Ca ) channel opener, were diminished in diabetic rats. Currently, few agents ameliorate the impaired vasodilator responses of retinal blood vessels. Our recent finding that the intravenous infusion of L-citrulline dilated retinal arterioles, suggests that L-citrulline could be a potential therapeutic agent for circulatory disorders of the retina. In this study, we determined the effect of an oral L-citrulline treatment on impaired acetylcholine- and BMS-191011-induced vasodilation in the retinal arterioles of diabetic rats. To induce diabetes, rats were administered an intravenous dose of streptozotocin (65 mg/kg) and a 5% D-glucose solution as drinking water. The L-citrulline (2 g/kg/day) and L-arginine (2 g/kg/day) treatments commenced either 15 days before or just after the streptozotocin injection and continued throughout the experimental period. A 29-day treatment with L-citrulline, but not L-arginine, significantly ameliorated the impaired acetylcholine- and BMS-191011-induced retinal vasodilation in diabetic rats without affecting their plasma glucose levels. The 2-week L-citrulline treatment tended to ameliorate the dysfunction of the acetylcholine-induced retinal vasodilation in diabetic rats. In conclusion, these results showed that the retinal blood vessel dysfunction induced by diabetes mellitus could be prevented by the long-term administration of L-citrulline and suggest that the latter could play a potentially prophylactic role in diabetic retinopathy.

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Role of Neuron–Glia Signaling in Regulation of Retinal Vascular Tone in Rats

Cited by 9 publications

References 25 publications

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

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

The “Neuro-Glial-Vascular” Unit: The Role of Glia in Neurovascular Unit Formation and Dysfunction

L-Citrulline ameliorates the attenuation of acetylcholine-induced vasodilation of retinal arterioles in diabetic rats

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