ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 49 citations in OpenAlex.
- Models of hyperglycaemia in diabetes mellitus and its complications.Nature reviews. Endocrinology · 2026Review
- The Mechanism of G Protein-Coupled Receptor Regulation of Ferroptosis in Hepatic Ischemia-Reperfusion Injury.International journal of molecular sciences · 2026Review
- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- α1D Adrenergic Receptor Antagonism Protects Against High Glucose-Induced Mitochondrial Dysfunction and Blood Retinal Barrier Breakdown in ARPE-19 Cells.International journal of molecular sciences · 2025Article
- Manifestation of Pathology in Animal Models of Diabetic Retinopathy Is Delayed from the Onset of Diabetes.International journal of molecular sciences · 2024Review
- Adrenoceptors in the Eye - Physiological and Pathophysiological Relevance.Handbook of experimental pharmacology · 2024Review
- Neurovascular Cell Death and Therapeutic Strategies for Diabetic Retinopathy.International journal of molecular sciences · 2023Review
- CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice.Diabetologia · 2023Article
- Towards a New Biomarker for Diabetic Retinopathy: Exploring RBP3 Structure and Retinoids Binding for Functional Imaging of Eyes In Vivo.International journal of molecular sciences · 2023Review
- The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells.The open biochemistry journal · 2022Article
- The serotonergic system dysfunction in diabetes mellitus.Frontiers in cellular neuroscience · 2022Review
- Regulation of Adrenergic, Serotonin, and Dopamine Receptors to Inhibit Diabetic Retinopathy: Monotherapies versus Combination Therapies.Molecular pharmacology · 2021Article
- Photoreceptor Cell Calcium Dysregulation and Calpain Activation Promote Pathogenic Photoreceptor Oxidative Stress and Inflammation in Prodromal Diabetic Retinopathy.The American journal of pathology · 2021Article
- Article
- Photoreceptor cells and RPE contribute to the development of diabetic retinopathy.Progress in retinal and eye research · 2021Review
- Sildenafil-evoked photoreceptor oxidative stress in vivo is unrelated to impaired visual performance in mice.PloS one · 2021Article
- Preventing diabetic retinopathy by mitigating subretinal space oxidative stressVisual neuroscience · 2020Review
- Impairment of Autophagy Causes Superoxide Formation and Caspase Activation in 661 W Cells, a Cell Line for Cone Photoreceptors, under Hyperglycemic Conditions.International journal of molecular sciences · 2020Article
- Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy.PloS one · 2020Article
- Neutrophil elastase contributes to the pathological vascular permeability characteristic of diabetic retinopathy.Diabetologia · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Reactive oxygen species play an important role in the pathogenesis of diabetic retinopathy. We studied the role of adrenergic and serotonin receptors in the generation of superoxide by retina and 661W retinal cells in high glucose and of the α1-adrenergic receptor (AR) on vascular lesions of the retinopathy in experimentally diabetic C57Bl/6J mice (and controls) after 2 and 8 months. Compared with 5 mM glucose, incubating cells or retinal explants in 30 mM glucose induced superoxide generation. This response was reduced or ablated by pharmacologic inhibition of the α1-AR (a Gq-coupled receptor) or Gs-coupled serotonin (5-HT2, 5-HT4, 5-HT6, and 5-HT7) receptors or by activation of the Gi-coupled α2-AR. In elevated glucose, the α1-AR produced superoxide via phospholipase C, inositol triphosphate-induced Ca(2+) release, and NADPH oxidase, and pharmacologic inhibition of these reactions prevented the superoxide increase. Generation of retinal superoxide, expression of proinflammatory proteins, and degeneration of retinal capillaries in diabetes all were significantly inhibited with daily doxazosin or apocynin (inhibitors of α1-AR and NADPH oxidase, respectively), but increased vascular permeability was not significantly affected. Adrenergic receptors, and perhaps other GPCRs, represent novel targets for inhibiting the development of important features of diabetic retinopathy.
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