Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System
Joint Authors
Dal Monte, Massimo
Rusciano, Dario
Cammalleri, Maurizio
Locri, Filippo
Marsili, Stefania
Lista, Liliana
De Rosa, Mario
Pavone, Vincenzo
Bagnoli, Paola
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-12-31
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
The spontaneously diabetic Torii (SDT) rat is of increasing preclinical interest because of its similarities to human type 2 diabetic retinopathy (DR).
The system formed by urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is a player in blood-retinal barrier (BRB) breakdown in DR.
Here, we investigated whether in SDT rats, preventive administration of UPARANT, an inhibitor of the uPAR pathway, counteracts the retinal impairment in response to chronic hyperglycemia.
Electroretinogram (ERG) monitoring was followed over time.
Fluorescein-dextran microscopy, CD31 immunohistochemistry, quantitative PCR, ELISA, Evans blue perfusion, and Western blot were also used.
UPARANT prevented ERG dysfunction, upregulation of vascular endothelial growth factor and fibroblast growth factor-2, BRB leakage, gliosis, and retinal cell death.
The mechanisms underlying UPARANT benefits were studied comparing them with the acute streptozotocin (STZ) model in which UPARANT is known to inhibit DR signs.
In SDT rats, but not in the STZ model, UPARANT downregulated the expression of uPAR and its membrane partners.
In both models, UPARANT reduced the levels of transcription factors coupled to inflammation or inflammatory factors themselves.
These findings may help to establish the uPAR system as putative target for the development of novel drugs that may prevent type 2 DR.
American Psychological Association (APA)
Cammalleri, Maurizio& Dal Monte, Massimo& Locri, Filippo& Marsili, Stefania& Lista, Liliana& De Rosa, Mario…[et al.]. 2017. Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System. Journal of Diabetes Research،Vol. 2017, no. 2017, pp.1-18.
https://search.emarefa.net/detail/BIM-1174029
Modern Language Association (MLA)
Cammalleri, Maurizio…[et al.]. Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System. Journal of Diabetes Research No. 2017 (2017), pp.1-18.
https://search.emarefa.net/detail/BIM-1174029
American Medical Association (AMA)
Cammalleri, Maurizio& Dal Monte, Massimo& Locri, Filippo& Marsili, Stefania& Lista, Liliana& De Rosa, Mario…[et al.]. Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System. Journal of Diabetes Research. 2017. Vol. 2017, no. 2017, pp.1-18.
https://search.emarefa.net/detail/BIM-1174029
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1174029