scholarly journals Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature

2013 ◽  
Vol 33 (11) ◽  
pp. 1685-1695 ◽  
Author(s):  
Eric A Newman
Keyword(s):  
Blood Flow ◽  
Glial Cells ◽  
Neurovascular Coupling ◽  
Retinal Blood Flow ◽  
Retinal Vasculature ◽  
Functional Hyperemia ◽  
Cellular Mechanisms ◽  
Neuronal Stimulation ◽  
Health And Disease ◽  
Coupling Mechanisms

The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed.

Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

1994 ◽  
Vol 72 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Daniel Abran ◽  
Daya R. Varma ◽  
Ding-You Li ◽  
Sylvain Chemtob
Keyword(s):  
Blood Flow ◽  
Receptor Agonist ◽  
Perfusion Pressure ◽  
Retinal Blood Flow ◽  
Receptor Subtype ◽  
Retinal Vasculature ◽  
Receptor Subtypes ◽  
Retinal Vessels ◽  
Limit Blood Flow ◽  
Arteries And Veins

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

scholarly journals Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

2015 ◽  
Vol 370 (1672) ◽  
pp. 20140195 ◽  
Author(s):  
Eric A. Newman
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Glial Cells ◽  
Neuronal Activity ◽  
Neurovascular Coupling ◽  
Müller Cells ◽  
Future Research ◽  
Prostaglandin E ◽  
Sk Channels ◽  
Muller Cells

Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. As reviewed in this article, Müller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Müller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca 2+ -activated K + (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E 2 (PGE 2 ) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells.

Regulation of blood flow in diabetic retinopathy

2020 ◽  
Vol 37 ◽  
Author(s):  
Amy R. Nippert ◽  
Eric A. Newman
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Neuronal Activity ◽  
Neurovascular Coupling ◽  
Functional Hyperemia ◽  
Retinal Neurons ◽  
Adequate Supply ◽  
Oxygen Levels ◽  
Signaling Mechanisms ◽  
Diabetic Brain

Abstract Blood flow in the retina increases in response to light-evoked neuronal activity, ensuring that retinal neurons receive an adequate supply of oxygen and nutrients as metabolic demands vary. This response, termed “functional hyperemia,” is disrupted in diabetic retinopathy. The reduction in functional hyperemia may result in retinal hypoxia and contribute to the development of retinopathy. This review will discuss the neurovascular coupling signaling mechanisms that generate the functional hyperemia response in the retina, the changes to neurovascular coupling that occur in diabetic retinopathy, possible treatments for restoring functional hyperemia and retinal oxygen levels, and changes to functional hyperemia that occur in the diabetic brain.

scholarly journals Role of Glial Cells in Regulating Retinal Blood Flow During Flicker-Induced Hyperemia in Cats

2015 ◽  
Vol 56 (12) ◽  
pp. 7551 ◽  
Author(s):  
Youngseok Song ◽  
Taiji Nagaoka ◽  
Takafumi Yoshioka ◽  
Seigo Nakabayashi ◽  
Tomofumi Tani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glial Cells ◽  
Retinal Blood Flow

scholarly journals Retinal Neurovascular Coupling in Diabetes

2020 ◽  
Vol 9 (9) ◽  
pp. 2829 ◽  
Author(s):  
Gerhard Garhöfer ◽  
Jacqueline Chua ◽  
Bingyao Tan ◽  
Damon Wong ◽  
Doreen Schmidl ◽  
...  
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Visual Stimulation ◽  
Neurovascular Coupling ◽  
Neural Tissue ◽  
Current Evidence ◽  
Compelling Evidence ◽  
Functional Hyperemia ◽  
Patients With Diabetes

Neurovascular coupling, also termed functional hyperemia, is one of the physiological key mechanisms to adjust blood flow in a neural tissue in response to functional activity. In the retina, increased neural activity, such as that induced by visual stimulation, leads to the dilatation of retinal arterioles, which is accompanied by an immediate increase in retinal and optic nerve head blood flow. According to the current scientific view, functional hyperemia ensures the adequate supply of nutrients and metabolites in response to the increased metabolic demand of the neural tissue. Although the molecular mechanisms behind neurovascular coupling are not yet fully elucidated, there is compelling evidence that this regulation is impaired in a wide variety of neurodegenerative and vascular diseases. In particular, it has been shown that the breakdown of the functional hyperemic response is an early event in patients with diabetes. There is compelling evidence that alterations in neurovascular coupling precede visible signs of diabetic retinopathy. Based on these observations, it has been hypothesized that a breakdown of functional hyperemia may contribute to the retinal complications of diabetes such as diabetic retinopathy or macular edema. The present review summarizes the current evidence of impaired neurovascular coupling in patients with diabetes. In this context, the molecular mechanisms of functional hyperemia in health and disease will be covered. Finally, we will also discuss how neurovascular coupling may in future be used to monitor disease progression or risk stratification.

scholarly journals Theoretical predictions of metabolic flow regulation in the retina

2016 ◽  
Vol 1 (2) ◽  
pp. 70-78
Author(s):  
Simone Cassani ◽  
Julia Arciero ◽  
Giovanna Guidoboni ◽  
Brent Siesky ◽  
Alon Harris
Keyword(s):  
Blood Flow ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Retinal Blood Flow ◽  
Regulatory Mechanisms ◽  
Tissue Oxygen ◽  
Theoretical Predictions ◽  
Health And Disease ◽  
Experimental Findings ◽  
Different Levels

Purpose: This study uses a theoretical model to investigate the response of retinal blood flow to changes in tissue oxygen demand. The study is motivated by the need for a better understanding of metabolic flow regulation mechanisms in health and disease.Methods: A mathematical model is used to calculate retinal blood flow for different levels of tissue oxygen demand in the presence or absence of regulatory mechanisms. The model combines a compartmental view of the retinal vasculature and a Krogh cylinder description for oxygen delivery to retinal tissue.Results: The model predicts asymmetric behavior in response to changes in tissue oxygen demand. When all regulatory mechanisms are active, the model predicts a 6% decrease in perfusion when tissue oxygen demand is decreased by 50% and a 23% increase in perfusion when tissue oxygen demand is increased by 50%. In the absence of metabolic and carbon dioxide responses, the model predicts a constant level of blood flow that does not respond to changes in oxygen demand, suggesting the importance of these two response mechanisms. The model is not able to replicate the increase in oxygen venous saturation that has been observed in some flicker stimulation studies.Conclusions: The increase in blood flow predicted by the model due to an increase in oxygen demand is not in the same proportion as the change in blood flow observed with the same decrease in oxygen demand, suggesting that vascular regulatory mechanisms may respond differently to different levels of oxygen demand. These results might be useful for interpreting clinical and experimental findings in health and disease.

Regulation of retinal blood flow in health and disease

2008 ◽  
Vol 27 (3) ◽  
pp. 284-330 ◽  
Author(s):  
Constantin J. Pournaras ◽  
Elisabeth Rungger-Brändle ◽  
Charles E. Riva ◽  
Sveinn H. Hardarson ◽  
Einar Stefansson
Keyword(s):  
Blood Flow ◽  
Retinal Blood Flow ◽  
Health And Disease

scholarly journals Prostaglandin E2 Dilates Intracerebral Arterioles When Applied to Capillaries: Implications for Small Vessel Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Amanda C. Rosehart ◽  
Thomas A. Longden ◽  
Nick Weir ◽  
Jackson T. Fontaine ◽  
Anne Joutel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Laser Scanning ◽  
Small Vessel Disease ◽  
Ex Vivo ◽  
Neurovascular Coupling ◽  
Laser Scanning Microscopy ◽  
Small Vessel ◽  
Prostaglandin E ◽  
Functional Hyperemia ◽  
Flow Measurements

Prostaglandin E2 (PGE2) has been widely proposed to mediate neurovascular coupling by dilating brain parenchymal arterioles through activation of prostanoid EP4 receptors. However, our previous report that direct application of PGE2 induces an EP1-mediated constriction strongly argues against its direct action on arterioles during neurovascular coupling, the mechanisms sustaining functional hyperemia. Recent advances have highlighted the role of capillaries in sensing neuronal activity and propagating vasodilatory signals to the upstream penetrating parenchymal arteriole. Here, we examined the effect of capillary stimulation with PGE2 on upstream arteriolar diameter using an ex vivo capillary-parenchymal arteriole preparation and in vivo cerebral blood flow measurements with two-photon laser-scanning microscopy. We found that PGE2 caused upstream arteriolar dilation when applied onto capillaries with an EC50 of 70 nM. The response was inhibited by EP1 receptor antagonist and was greatly reduced, but not abolished, by blocking the strong inward-rectifier K+ channel. We further observed a blunted dilatory response to capillary stimulation with PGE2 in a genetic mouse model of cerebral small vessel disease with impaired functional hyperemia. This evidence casts previous findings in a different light, indicating that capillaries are the locus of PGE2 action to induce upstream arteriolar dilation in the control of brain blood flow, thereby providing a paradigm-shifting view that nonetheless remains coherent with the broad contours of a substantial body of existing literature.

Sign in / Sign up

Export Citation Format

Share Document