Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit
Background: Diabetic retinopathy (DR) remains one of the most common complications of diabetes despite great efforts to uncover its underlying mechanisms. The pathogenesis of DR is characterized by the deterioration of the neurovascular unit (NVU), showing damage of vascular cells, activation of gli...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877823000704 |
| _version_ | 1797796471271063552 |
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| author | Yixin Wang Rachana Eshwaran Susanne C. Beck Hans-Peter Hammes Thomas Wieland Yuxi Feng |
| author_facet | Yixin Wang Rachana Eshwaran Susanne C. Beck Hans-Peter Hammes Thomas Wieland Yuxi Feng |
| author_sort | Yixin Wang |
| collection | DOAJ |
| description | Background: Diabetic retinopathy (DR) remains one of the most common complications of diabetes despite great efforts to uncover its underlying mechanisms. The pathogenesis of DR is characterized by the deterioration of the neurovascular unit (NVU), showing damage of vascular cells, activation of glial cells and dysfunction of neurons. Activation of the hexosamine biosynthesis pathway (HBP) and increased protein O-GlcNAcylation have been evident in the initiation of DR in patients and animal models. Scope of review: The impairment of the NVU, in particular, damage of vascular pericytes and endothelial cells arises in hyperglycemia-independent conditions as well. Surprisingly, despite the lack of hyperglycemia, the breakdown of the NVU is similar to the pathology in DR, showing activated HBP, altered O-GlcNAc and subsequent cellular and molecular dysregulation. Major conclusions: This review summarizes recent research evidence highlighting the significance of the HBP in the breakdown of the NVU in hyperglycemia-dependent and -independent manners, and thus identifies joint avenues leading to vascular damage as seen in DR and thus identifying novel potential targets in such retinal diseases. |
| first_indexed | 2024-03-13T03:33:36Z |
| format | Article |
| id | doaj.art-a23251ce674a49769a0bc78ae51febe2 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-03-13T03:33:36Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-a23251ce674a49769a0bc78ae51febe22023-06-24T05:16:24ZengElsevierMolecular Metabolism2212-87782023-07-0173101736Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unitYixin Wang0Rachana Eshwaran1Susanne C. Beck2Hans-Peter Hammes3Thomas Wieland4Yuxi Feng5Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyExperimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyDivision of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany5th Medical Department, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyExperimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, GermanyExperimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Corresponding author. Experimental Pharmacology Mannheim, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany.Background: Diabetic retinopathy (DR) remains one of the most common complications of diabetes despite great efforts to uncover its underlying mechanisms. The pathogenesis of DR is characterized by the deterioration of the neurovascular unit (NVU), showing damage of vascular cells, activation of glial cells and dysfunction of neurons. Activation of the hexosamine biosynthesis pathway (HBP) and increased protein O-GlcNAcylation have been evident in the initiation of DR in patients and animal models. Scope of review: The impairment of the NVU, in particular, damage of vascular pericytes and endothelial cells arises in hyperglycemia-independent conditions as well. Surprisingly, despite the lack of hyperglycemia, the breakdown of the NVU is similar to the pathology in DR, showing activated HBP, altered O-GlcNAc and subsequent cellular and molecular dysregulation. Major conclusions: This review summarizes recent research evidence highlighting the significance of the HBP in the breakdown of the NVU in hyperglycemia-dependent and -independent manners, and thus identifies joint avenues leading to vascular damage as seen in DR and thus identifying novel potential targets in such retinal diseases.http://www.sciencedirect.com/science/article/pii/S2212877823000704Hexosamine biosynthetic pathwayRetinal neurovascular unitHyperglycemiaO-GlcNAcEndothelial cellPericyte |
| spellingShingle | Yixin Wang Rachana Eshwaran Susanne C. Beck Hans-Peter Hammes Thomas Wieland Yuxi Feng Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit Molecular Metabolism Hexosamine biosynthetic pathway Retinal neurovascular unit Hyperglycemia O-GlcNAc Endothelial cell Pericyte |
| title | Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit |
| title_full | Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit |
| title_fullStr | Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit |
| title_full_unstemmed | Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit |
| title_short | Contribution of the hexosamine biosynthetic pathway in the hyperglycemia-dependent and -independent breakdown of the retinal neurovascular unit |
| title_sort | contribution of the hexosamine biosynthetic pathway in the hyperglycemia dependent and independent breakdown of the retinal neurovascular unit |
| topic | Hexosamine biosynthetic pathway Retinal neurovascular unit Hyperglycemia O-GlcNAc Endothelial cell Pericyte |
| url | http://www.sciencedirect.com/science/article/pii/S2212877823000704 |
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