Abstract
Objective:
To examine the mechanisms of Nogo-B (RTN4B) in the protection of blood-retinal barrier in experimental diabetic retinopathy.
Methods:
The level of Nogo-B in vitreous and plasma samples was detected with ELISA. Diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. The rats were injected intravitreally with adeno-associated virus (AAV) for knockdown the expression of Nogo-B in retina or/and as AAV negative control. The permeability of blood-retinal barrier was detected with Rhodamine-B-dextran leakage assay. The expressions of Nogo-B, junctional proteins, inflammatory factors and signaling pathways were examined with Western blot and quantitative real-time PCR.
Results:
Nogo-B expression was significantly upregulated in clinical samples and experimental diabetic rat models. Under normal condition, Nogo-B knockdown resulted in the increased permeability of retinal blood vessels. In diabetic rat retinas, the vascular leakage was increased significantly, which was partially decreased by Nogo-B knockdown through increasing p/t-Src (Tyr529) and p/t-Akt (Ser473), and decreasing p/t-ERK1/2.
Conclusion:
Nogo-B was increased in diabetic retinopathy and silencing Nogo-B is a promising therapy for diabetic retinopathy.
Keywords:
Blood-retinal barrier; Diabetic retinopathy; ERK; Nogo-B (RTN4B); Src/Akt.
Copyright © 2021 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood-Retinal Barrier / metabolism
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / genetics*
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Diabetes Mellitus, Experimental / metabolism
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Diabetic Retinopathy / genetics*
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Diabetic Retinopathy / metabolism
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Diabetic Retinopathy / pathology
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Diabetic Retinopathy / therapy
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Gene Expression Regulation
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Male
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphatidylinositol 3-Kinases / genetics*
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / genetics*
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Receptors, Cell Surface / metabolism
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Retina / metabolism
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Retina / pathology
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Retinal Vessels / metabolism
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Retinal Vessels / pathology
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Signal Transduction
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Streptozocin / administration & dosage
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src-Family Kinases / genetics*
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src-Family Kinases / metabolism
Substances
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Nus1 protein, rat
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RNA, Small Interfering
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Receptors, Cell Surface
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Streptozocin
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src-Family Kinases
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Proto-Oncogene Proteins c-akt
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Mapk1 protein, rat
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3