mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Vascular Expression of Permeability-Resistant Occludin Mutant Preserves Visual
Function in Diabetes.
Authors Goncalves A, Dreffs A, Lin CM, Sheskey S, Hudson N, Keil J, Campbell M,
Antonetti DA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Diabetes
Year 2021
Date Published 7/1/2021
Volume : Pages 70 : 1549 - 1560
PubMed Reference 33883214
Abstract 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.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.