Vascular Expression of Permeability-Resistant Occludin Mutant Preserves Visual Function in Diabetes Article Swipe
Andreia Gonçalves
,
Alyssa Dreffs
,
Cheng‐mao Lin
,
Sarah Sheskey
,
Natalie Hudson
,
Jason M. Keil
,
Matthew Campbell
,
David A. Antonetti
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.2337/db20-1220
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.2337/db20-1220
Diabetic retinopathy is one of the leading causes of vision loss and blindness. Extensive preclinical and clinical evidence exists for both vascular and neuronal pathology. However, the relationship of these changes in the neurovascular unit and impact on vision remains to be determined. Here, we investigate the role of tight junction protein occludin phosphorylation at S490 in modulating barrier properties and its impact on visual function. Conditional vascular expression of the phosphorylation-resistant Ser490 to Ala (S490A) form of occludin preserved tight junction organization and reduced vascular endothelial growth factor (VEGF)-induced permeability and edema formation after intraocular injection. In the retinas of streptozotocin-induced diabetic mice, endothelial-specific expression of the S490A form of occludin completely prevented diabetes-induced permeability to labeled dextran and inhibited leukostasis. Importantly, vascular-specific expression of the occludin mutant completely blocked the diabetes-induced decrease in visual acuity and contrast sensitivity. Together, these results reveal that occludin acts to regulate barrier properties downstream of VEGF in a phosphorylation-dependent manner and that loss of inner blood-retinal barrier integrity induced by diabetes contributes to vision loss.
Related Topics
Concepts
Occludin
Tight junction
Vascular permeability
Blood–retinal barrier
Vascular endothelial growth factor
Barrier function
Phosphorylation
Diabetic retinopathy
Cell biology
Retina
Leukostasis
Blood–brain barrier
Edema
Diabetes mellitus
Biology
Retinal
Endocrinology
Internal medicine
Medicine
Ophthalmology
Neuroscience
VEGF receptors
Central nervous system
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.2337/db20-1220
- https://diabetesjournals.org/diabetes/article-pdf/70/7/1549/628427/db201220.pdf
- OA Status
- bronze
- Cited By
- 23
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3154311708
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3154311708Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.2337/db20-1220Digital Object Identifier
- Title
-
Vascular Expression of Permeability-Resistant Occludin Mutant Preserves Visual Function in DiabetesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-21Full publication date if available
- Authors
-
Andreia Gonçalves, Alyssa Dreffs, Cheng‐mao Lin, Sarah Sheskey, Natalie Hudson, Jason M. Keil, Matthew Campbell, David A. AntonettiList of authors in order
- Landing page
-
https://doi.org/10.2337/db20-1220Publisher landing page
- PDF URL
-
https://diabetesjournals.org/diabetes/article-pdf/70/7/1549/628427/db201220.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://diabetesjournals.org/diabetes/article-pdf/70/7/1549/628427/db201220.pdfDirect OA link when available
- Concepts
-
Occludin, Tight junction, Vascular permeability, Blood–retinal barrier, Vascular endothelial growth factor, Barrier function, Phosphorylation, Diabetic retinopathy, Cell biology, Retina, Leukostasis, Blood–brain barrier, Edema, Diabetes mellitus, Biology, Retinal, Endocrinology, Internal medicine, Medicine, Ophthalmology, Neuroscience, VEGF receptors, Central nervous systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
23Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 6, 2023: 5, 2022: 6, 2021: 2Per-year citation counts (last 5 years)
- References (count)
-
54Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.preserved | 79 |
| abstract_inverted_index.prevented | 113 |
| abstract_inverted_index.blindness. | 12 |
| abstract_inverted_index.completely | 112, 129 |
| abstract_inverted_index.downstream | 151 |
| abstract_inverted_index.expression | 68, 105, 124 |
| abstract_inverted_index.injection. | 96 |
| abstract_inverted_index.modulating | 57 |
| abstract_inverted_index.pathology. | 24 |
| abstract_inverted_index.properties | 59, 150 |
| abstract_inverted_index.Conditional | 66 |
| abstract_inverted_index.contributes | 169 |
| abstract_inverted_index.determined. | 42 |
| abstract_inverted_index.endothelial | 86 |
| abstract_inverted_index.intraocular | 95 |
| abstract_inverted_index.investigate | 45 |
| abstract_inverted_index.preclinical | 14 |
| abstract_inverted_index.retinopathy | 1 |
| abstract_inverted_index.Importantly, | 122 |
| abstract_inverted_index.leukostasis. | 121 |
| abstract_inverted_index.organization | 82 |
| abstract_inverted_index.permeability | 90, 115 |
| abstract_inverted_index.relationship | 27 |
| abstract_inverted_index.sensitivity. | 139 |
| abstract_inverted_index.blood-retinal | 163 |
| abstract_inverted_index.neurovascular | 33 |
| abstract_inverted_index.(VEGF)-induced | 89 |
| abstract_inverted_index.phosphorylation | 53 |
| abstract_inverted_index.diabetes-induced | 114, 132 |
| abstract_inverted_index.vascular-specific | 123 |
| abstract_inverted_index.endothelial-specific | 104 |
| abstract_inverted_index.streptozotocin-induced | 101 |
| abstract_inverted_index.phosphorylation-dependent | 156 |
| abstract_inverted_index.phosphorylation-resistant | 71 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 93 |
| corresponding_author_ids | https://openalex.org/A5006745683 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 8 |
| corresponding_institution_ids | https://openalex.org/I27837315 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8199999928474426 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.84900317 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |