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Identifier |
000389943 |
Title |
Molecular inflammatory factors in diabetic retinopathy : role of azurocidin |
Alternative Title |
Μοριακοί παράγοντες φλεγμονής στη διαβητική αμφιβληστροειδοπάθεια: |
Author
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Σκόνδρα, Δήμητρα
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Thesis advisor
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Τσιλιμπάρης, Μιλτιάδης
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Reviewer
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Παπαβασιλείου, Ευστάθιος
Παλλήκαρης, Ιωάννης
Μπούμπας, Δημήτριος
Θερμού, Κυριακή
Γανωτάκης, Εμμανουήλ
Τσατσάνης, Χρήστος
|
Abstract |
PURPOSE. Azurocidin, released by neutrophils during leukocyte-endothelial
interaction, is a main cause of leukocyte-evoked vascular leakage. Its role in the
retina, however, is unknown.
METHODS. Brown Norway rats received intravitreal injections of azurocidin and
vehicle control. Blood-retinal barrier (BRB) breakdown was quantified using the
Evans blue (EB) dye technique 1, 3, and 24 hours after intravitreal injection. To
block azurocidin, aprotinin was injected intravenously before the intravitreal
injections. To investigate if azurocidin increases retinal leukostasis, number of
adherent leukocytes in the retina 2 hours and 24 hours after azurocidin injection
were quantified using the Concanavalin A perfusion technique. To investigate
whether azurocidin plays a role in vascular endothelial growth factor (VEGF)-
induced BRB breakdown, rats were treated intravenously with aprotinin, followed
by intravitreal injection of VEGF164. BRB breakdown was quantified 24 hours
later. To investigate whether azurocidin may mediate BRB breakdown in early
diabetes, aprotinin or vehicle was injected intravenously each day for 10 days to
streptozotocin-induced diabetic rats, and BRB breakdown was quantified. To
investigate whether azurocidin may mediate BRB breakdown in endotoxin
induced uveitis (EIU) as another model of leukocyte mediated retinal vascular
leakage , EIU rats were treated with aprotinin or vehicle and BRB breakdown
was quantified 24 hours after the EIU induction.
RESULTS. Intravitreal injection of azurocidin (20 μg) induced a 6.8-fold increase
in vascular permeability compared with control at 1–3 hours (P ΄&λτ 0.05), a 2.7-fold
increase at 3-5 hours (P ΄&λτ 0.01), and a 1.7-fold increase at 24 hours (P ΄&λτ 0.05).
Azurocidin did not increase static retinal leukostasis at 2 hours after the
intravitreal injection or 24 hours after the intravitreal injection. Aprotinin inhibited
azurocidin-induced BRB breakdown by 98% (P ΄&λλτ 0.05). Furthermore, treatment
with aprotinin significantly suppressed VEGF-induced BRB breakdown by 93% (P
΄&λτ 0.05) , BRB breakdown in early experimental diabetes by 40.6% (P ΄&λτ 0.05) and
BRB breakdown in EIU by 73% (P΄&λτ0.05)
CONCLUSIONS. Azurocidin increases retinal vascular permeability and is
effectively blocked by aprotinin. The inhibition of VEGF-induced, early diabetic
BRB breakdown and EIU retinal vascular leakage with aprotinin indicates that
azurocidin may be an important mediator of leukocyte-dependent BRB
breakdown especially in a disease model like diabetes that leukostasis is crucial
in pathogenesis. Azurocidin may become a new therapeutic target in the
treatment of retinal vascular leakage, diabetic retinopathy and diabetic macular
edema.
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Language |
English |
Subject |
Diabetic retinopathy |
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Inflammation |
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Διαβητική αμφιβληστροειδοπάθεια |
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Φλεγμονή |
Issue date |
2014-12-03 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/5/b/3/metadata-dlib-1423756791-421228-31132.tkl
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Views |
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