The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With Streptozotocin-Induced Diabetes
| العنوان: | The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With Streptozotocin-Induced Diabetes |
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| المؤلفون: | Antonis Kouvarakis, Haralambos E. Katerinopoulos, Sofia Papadogkonaki, Emmanuil Koulakis, Niki Mastrodimou, Achille Gravanis, Despina Kokona, Silvia Lisa, Ruth Ibán-Arias, Panagiota Iordanidou, Aggeliki Sotiriou, Myrto Fothiadaki, Kyriaki Thermos, Ioannis Charalampopoulos |
| المصدر: | Diabetes. 67:321-333 |
| بيانات النشر: | American Diabetes Association, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Anti-Inflammatory Agents, Nerve Tissue Proteins, Inflammation, Tropomyosin receptor kinase A, Receptor, Nerve Growth Factor, Retina, Streptozocin, Diabetes Mellitus, Experimental, Proinflammatory cytokine, Rats, Sprague-Dawley, 03 medical and health sciences, Ganglia, Sensory, Internal medicine, Internal Medicine, medicine, Animals, Phosphorylation, Receptor, trkA, Eye Proteins, Receptor, Diabetic Retinopathy, Dose-Response Relationship, Drug, Tyrosine hydroxylase, Chemistry, Dehydroepiandrosterone, Streptozotocin, Axons, Amacrine Cells, Neuroprotective Agents, 030104 developmental biology, Cytokine, Endocrinology, Apoptosis, Female, medicine.symptom, Neuroglia, Protein Processing, Post-Translational, medicine.drug |
| الوصف: | BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have antiapoptotic properties via mechanisms involving the nerve growth factor receptors (tropomyosin-related kinase A [TrkA]/neurotrophin receptor p75 [p75NTR]). In this study, we examined the effects of BNN27 on neural/glial cell function, apoptosis, and inflammation in the experimental rat streptozotocin (STZ) model of diabetic retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate p75NTR expression was investigated. BNN27 (2,10, and 50 mg/kg i.p. for 7 days) administration 4 weeks post–STZ injection (paradigm A) reversed the diabetes-induced glial activation and loss of function of amacrine cells (brain nitric oxide synthetase/tyrosine hydroxylase expression) and ganglion cell axons via a TrkA receptor (TrkAR)-dependent mechanism. BNN27 activated/phosphorylated the TrkAY490 residue in the absence but not the presence of TrkAR inhibitor and abolished the diabetes-induced increase in p75NTR expression. However, it had no effect on retinal cell death (TUNEL+ cells). A similar result was observed when BNN27 (10 mg/kg i.p.) was administered at the onset of diabetes, every other day for 4 weeks (paradigm B). However, BNN27 decreased the activation of caspase-3 in both paradigms. Finally, BNN27 reduced the proinflammatory (TNFα and IL-1β) and increased the anti-inflammatory (IL-10 and IL-4) cytokine levels. These findings suggest that BNN27 has the pharmacological profile of a therapeutic for DR, since it targets both the neurodegenerative and inflammatory components of the disease. |
| تدمد: | 1939-327X 0012-1797 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54f77a26a9443bdd806dbf357c4bb862 https://doi.org/10.2337/db17-0391 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....54f77a26a9443bdd806dbf357c4bb862 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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