scholarly journals Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 761 ◽  
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Aytan Musayeva ◽  
Adrian Gericke
Keyword(s):  
Intracellular Signaling ◽  
Vascular Reactivity ◽  
Vascular System ◽  
Vascular Dysfunction ◽  
Special Focus ◽  
Retinal Diseases ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Pathophysiological Role ◽  
Neuron Function

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.

Omega-3E treatment regulates matrix metalloproteinases and prevents vascular reactivity alterations in diabetic rat aortaThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 1063-1073 ◽  
Author(s):  
Esma N. Zeydanli ◽  
Belma Turan
Keyword(s):  
Matrix Metalloproteinases ◽  
Vascular Reactivity ◽  
Vascular System ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Close Correlation ◽  
Tissue Level ◽  
Rat Aorta ◽  
Diabetic Rat ◽  
Cardiovascular Research

It is known that increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. Although a close correlation exists between increased oxidative stress and the activation of matrix metalloproteinases (MMPs), little is known about the effect of hyperglycemia on the regulation and contribution of MMPs in the vascular system. Therefore, we aimed to examine whether omega-3E (50 mg/kg per day for 4 weeks), a long-chain (n-3) polyunsaturated fatty acid enriched with vitamin E, has a beneficial effect on vascular dysfunction via affecting MMPs in streptozotocin-diabetic rat aorta. Omega-3E treatment improved the diabetes-induced impairment of phenylephrine-induced contraction and isoproterenol-induced relaxation responses of aorta. It also exhibited marked protection against diabetes-induced degenerative changes in smooth muscle cell morphology. Biochemical data showed that this treatment significantly prevented important changes, such as inhibition of MMP-2 and MMP-9 activity, loss of tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) protein, increase in tissue levels of thiol oxidation, endothelin-1, protein kinase C (PKC), and cAMP production, and decrease in tissue level of nitrite. These results indicated that omega-3E significantly improved impaired vascular responses and regulated the activity of MMPs via preventing oxidative injury. Overall, the data suggest that omega-3E ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for omega-3E’s potential as a therapeutic agent for the prevention of vascular disorders in diabetes.

Beneficial effects of isometric strength training on endothelial dysfunction in rats

2006 ◽  
Vol 31 (5) ◽  
pp. 621-630 ◽  
Author(s):  
Hélène Figard ◽  
Vincent Gaume ◽  
Fabienne Mougin ◽  
Céline Demougeot ◽  
Alain Berthelot
Keyword(s):  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Isometric Exercise ◽  
Ovariectomized Rats ◽  
Daily Injection ◽  
Sprague Dawley ◽  
Estradiol Treatment ◽  
Sedentary Group ◽  
Age Related ◽  
17Β Estradiol

Using female 4-week-old Sprague–Dawley rats, we investigated the effects of 14 weeks of progressive strength isometric training on endothelium dysfunction after estrogen deficiency. We also proposed possible mechanism(s) by which such training acted on endothelium-dependent vasodilation in thoracic aortic rings. Rats were randomly divided into 4 groups of 8 rats: a sham operated group, an ovariectomized sedentary group receiving 17β-estradiol vehicle s.c. daily, an ovariectomized sedentary group receiving a daily injection of 20 µg·kg–1 17β-estradiol s.c., and an ovariectomized exercised group receiving daily s.c. vehicle. Vascular reactivity of aortic rings have been evaluated by a cumulative dose of acetylcholine (ACh), in the presence or absence of l-NAME (N-nitro-l-arginine methyl ester), indomethacin, thapsigargin, iberiotoxin, apamin, and tetraethylammonium. Ovariectomy markedly decreased the relaxation caused by ACh, whereas 17β-estradiol treatment induced a significant increase in the relaxation elicited by ACh. Isometric exercise enhanced relaxation due to ACh. This enhancement was attenuated in the presence of l-NAME, indomethacin, thapsigargin, iberiotoxin, and apamin. Our data indicated, for the first time, that the endothelium-dependent relaxant response to ACh was markedly improved in trained ovariectomized rats. This increased vasodilation is mediated by nitric oxide, cyclooxygenase, sarco-endoplasmic reticulum Ca2+-ATPase pathways, and endothelium-derived hyperpolarizing factor. Finally, this study suggested that resistance training may provide benefits in addressing vascular dysfunction consequent to a decline in estrogen levels after menopause. However, any benefits for age-related vascular dysfunction remain to be demonstrated.

scholarly journals Healthberry 865® and Its Related, Specific, Single Anthocyanins Exert a Direct Vascular Action, Modulating Both Endothelial Function and Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1191
Author(s):  
Albino Carrizzo ◽  
Rosario Lizio ◽  
Paola Di Pietro ◽  
Michele Ciccarelli ◽  
Antonio Damato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Intracellular Signaling ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Epidemiological Studies ◽  
Direct Role ◽  
And Oxidative Stress

In recent years, epidemiological studies have identified a relationship between diet and cerebro–cardiovascular disease (CVD). In this regard, there is a promising dietary group for cardiovascular protection are polyphenols, especially anthocyanins. Vascular reactivity studies were performed using Healthberry 865® and constituent single anthocyanins to characterize vasomotor responses; immunofluorescence analysis with dichlorofluorescein diacetate and dihydroethidium were used to evaluate nitric oxide and oxidative stress; lucigenin assay was used to measure NADPH oxidase activity; and gel electrophoresis and immunoblotting were used to dissect the molecular mechanisms involved. We demonstrated that Healthberry 865® exerts an important vasorelaxant effect of resistance artery functions in mice. Its action is mediated by nitric oxide release through the intracellular signaling PI3K/Akt. Moreover, behind its capability of modulating vascular tone, it also exerts an important antioxidant effect though the modulation of the NADPH oxidase enzyme. Interestingly, its cardiovascular properties are mediated by the selective action of different anthocyanins. Finally, the exposure of human dysfunctional vessels to Healthberry 865® significantly reduces oxidative stress and improves NO bioavailability. Although further investigations are needed, our data demonstrate the direct role of Healthberry 865® on the modulation of vasculature, both on the vasorelaxation and on oxidative stress; thus, supporting the concept that a pure mixture of anthocyanins could be helpful in preventing the onset of vascular dysfunction associated with the development of CVD.

scholarly journals Relation between Regional Functional MRI Activation and Vascular Reactivity to Carbon Dioxide during Normal Aging

2003 ◽  
Vol 23 (5) ◽  
pp. 565-573 ◽  
Author(s):  
Axel Riecker ◽  
Wolfgang Grodd ◽  
Uwe Klose ◽  
Jorg B. Schulz ◽  
Klaus Gröschel ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Vascular System ◽  
Blood Oxygenation ◽  
Finger Tapping ◽  
Breath Holding ◽  
Bold Signal ◽  
Cerebral Activation ◽  
Age Related ◽  
Older Subjects ◽  
Young Subjects

Recent blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging studies have shown a reduction of cerebral activation during aging, which may be associated with age-related changes of the cerebral vascular system. The authors used a global hypercapnic breath-holding challenge to define nonneuronal contributions to a significantly reduced activation in the primary sensorimotor cortex during finger tapping in a group of old (n = 6; mean age 65 years) compared with a group of young (n = 6; mean age 27 years) subjects. Within significantly activated voxels in both groups during finger tapping, the mean BOLD signal amplitudes were significantly smaller in the group of older subjects for both tasks. In those voxels showing significant activation only in young subjects during finger tapping, the response to hypercapnia was also greatly diminished in older subjects. The attenuated hypercapnic BOLD signal response in older subjects within this region suggests that age-dependent changes of the cerebral vasculature may alter the neuronal–vascular coupling. In older subjects, cerebral vessels may not react as effectively in response to a vasodilating stimulus, which will lead to differences in the number of voxels that pass a criterion threshold despite similar neuronal activation.

scholarly journals Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093422 ◽  
Author(s):  
Michael N. Moore
Keyword(s):  
Intracellular Signaling ◽  
Adenosine Monophosphate ◽  
Target Of Rapamycin ◽  
Cell Physiology ◽  
Mechanistic Target Of Rapamycin ◽  
Age Related ◽  
Mechanistic Basis ◽  
The Many ◽  
Mtor Complex 1

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals The Insect Type 1 Tyramine Receptors: From Structure to Behavior

Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 315
Author(s):  
Luca Finetti ◽  
Thomas Roeder ◽  
Girolamo Calò ◽  
Giovanni Bernacchia
Keyword(s):  
Intracellular Signaling ◽  
Physiological Role ◽  
Basic Structure ◽  
Special Focus ◽  
Behavioral Traits ◽  
Physiological Relevance ◽  
Transduction Mechanisms ◽  
Octopamine Receptor ◽  
Available Information ◽  
First Time

Tyramine is a neuroactive compound that acts as neurotransmitter, neuromodulator, and neurohormone in insects. Three G protein-coupled receptors, TAR1-3, are responsible for mediating the intracellular pathway in the complex tyraminergic network. TAR1, the prominent player in this system, was initially classified as an octopamine receptor which can also be activated by tyramine, while it later appeared to be a true tyramine receptor. Even though TAR1 is currently considered as a well-defined tyramine receptor and several insect TAR1s have been characterized, a defined nomenclature is still inconsistent. In the last years, our knowledge on the structural, biochemical, and functional properties of TAR1 has substantially increased. This review summarizes the available information on TAR1 from different insect species in terms of basic structure, its regulation and signal transduction mechanisms, and its distribution and functions in the brain and the periphery. A special focus is given to the TAR1-mediated intracellular signaling pathways as well as to their physiological role in regulating behavioral traits. Therefore, this work aims to correlate, for the first time, the physiological relevance of TAR1 functions with the tyraminergic system in insects. In addition, pharmacological studies have shed light on compounds with insecticidal properties having TAR1 as a target and on the emerging trend in the development of novel strategies for pest control.

Differential expression of α2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats

2004 ◽  
Vol 287 (1) ◽  
pp. H135-H148 ◽  
Author(s):  
Tsuneo Kobayashi ◽  
Takayuki Matsumoto ◽  
Kazuyuki Ooishi ◽  
Katsuo Kamata
Keyword(s):  
Vascular Reactivity ◽  
Matched Control ◽  
Early Stage ◽  
Vascular Dysfunction ◽  
Spontaneous Diabetes ◽  
Relaxation Response ◽  
No Production ◽  
Gk Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The aim of the present study was to compare vascular dysfunction between the early (12 wk old) and later (36 wk old) stages of spontaneous diabetes in Goto-Kakizaki (GK) rats. We also evaluated the aortic expression of the α2D-adrenoceptor and endothelial nitric oxide synthase (eNOS). Vascular reactivity was assessed in thoracic aortas from age-matched control rats and 12- and 36-wk GK rats. Using RT-PCR and immunoblots, we also examined the changes in expression of the α2D-adrenoceptor and eNOS. In aortas from GK rats (vs. those from age-matched control rats): 1) the relaxation response to ACh was enhanced at 12 wk but decreased at 36 wk; 2) the relaxation response to sodium nitroprusside was decreased at both 12 and 36 wk, 3) norepinephrine (NE)-induced contractility was decreased at 12 wk but not at 36 wk, 4) the expressions of α1B- and α1D-adrenoceptors were unaffected, whereas those of α2D-adrenoceptor and eNOS mRNAs were increased at both 12 and 36 wk; and 5) NE- and ACh-stimulated NOx (nitrite and nitrate) levels were increased at 12 wk, although at 36 wk ACh-stimulated NOx was lower, whereas NE-stimulated NOx showed no change. These results clearly demonstrate that enhanced ACh-induced relaxation and impaired NE-induced contraction, due to NO overproduction via eNOS and increased α2D-adrenoceptor expression, occur in early-stage GK rats and that the impaired ACh-induced relaxation in later-stage GK rats is due to reductions in both NO production and NO responsiveness (but not in eNOS expression).

scholarly journals The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1222
Author(s):  
Domitilla Mandatori ◽  
Letizia Pelusi ◽  
Valeria Schiavone ◽  
Caterina Pipino ◽  
Natalia Di Pietro ◽  
...  
Keyword(s):  
Bone Loss ◽  
Vascular Calcification ◽  
Vascular System ◽  
The Elderly ◽  
Food Supplement ◽  
Vitamin K2 ◽  
Bioactive Molecules ◽  
Calcium Deposition ◽  
Age Related

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

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