Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats
Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as pu...
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2022-12-01
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author | Dimitris Spyridakos Niki Mastrodimou Kiran Vemuri Thanh C. Ho Spyros P. Nikas Alexandros Makriyannis Kyriaki Thermos |
author_facet | Dimitris Spyridakos Niki Mastrodimou Kiran Vemuri Thanh C. Ho Spyros P. Nikas Alexandros Makriyannis Kyriaki Thermos |
author_sort | Dimitris Spyridakos |
collection | DOAJ |
description | Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease. |
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issn | 1661-6596 1422-0067 |
language | English |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-d0a713dbdfe34183af87614ededd306f2023-11-16T15:30:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124124010.3390/ijms24010240Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic RatsDimitris Spyridakos0Niki Mastrodimou1Kiran Vemuri2Thanh C. Ho3Spyros P. Nikas4Alexandros Makriyannis5Kyriaki Thermos6Department of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, GreeceDepartment of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, GreeceCenter for Drug Discovery, Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USACenter for Drug Discovery, Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USACenter for Drug Discovery, Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USACenter for Drug Discovery, Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USADepartment of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, GreeceOxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease.https://www.mdpi.com/1422-0067/24/1/240early stage diabetic retinopathyendocannabinoid systemcannabinoid receptorsneuroprotectioneye dropsnitrative stress |
spellingShingle | Dimitris Spyridakos Niki Mastrodimou Kiran Vemuri Thanh C. Ho Spyros P. Nikas Alexandros Makriyannis Kyriaki Thermos Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats International Journal of Molecular Sciences early stage diabetic retinopathy endocannabinoid system cannabinoid receptors neuroprotection eye drops nitrative stress |
title | Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats |
title_full | Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats |
title_fullStr | Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats |
title_full_unstemmed | Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats |
title_short | Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats |
title_sort | blockade of cb1 or activation of cb2 cannabinoid receptors is differentially efficacious in the treatment of the early pathological events in streptozotocin induced diabetic rats |
topic | early stage diabetic retinopathy endocannabinoid system cannabinoid receptors neuroprotection eye drops nitrative stress |
url | https://www.mdpi.com/1422-0067/24/1/240 |
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