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Identifier |
000421551 |
Title |
Neuroprotective Approaches in Experimental Models of Retinal Degeneration |
Alternative Title |
Νευροπροστατευτικές προσεγγίσεις σε πειραματικά μοντέλα νευροεκφύλισης του αμφιβληστροειδούς |
Author
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Τσόκα, Αικατερίνη -Παυλίνα
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Thesis advisor
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Τσιλιμπάρης, Μιλτιάδης
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Reviewer
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Θερμού, Κυριακή
Γραβάνης, Αχιλλέας
Καραγωγέως, Δόμνα
Τσατσάνης, Χρήστος
Μήτσιας, Παναγιώτης
Παλλήκαρης, Ιωάννης
|
Abstract |
BNN27, a blood-brain barrier-permeable, C17-spiroepoxy derivative of
dehydroepiandrosterone (DHEA) has shown promising neuroprotective activity through
interaction with nerve growth factor receptors, tropomyosin receptor kinase A (TrkA) and panneurotrophin
receptor p75NTR. In this study, we administered systemically BNN27 in two
murine models of acute retinal degeneration/injury; experimental retinal detachment (RD) that
results in photoreceptor cell death and N-methyl-D-aspartate (NMDA)-induced retinal
excitotoxicity that results in cell death primarily of the inner retina and the retinal ganglion
cells (RGCs). TUNEL+ (Terminal deoxynucleotidyl transferase -TdT- dUTP Nick-End
Labeling) photoreceptors were significantly decreased 24 hours post RD after a single
administration of 200 mg/kg BNN27. Furthermore, BNN27 increased inflammatory cell
infiltration, as well as, two markers of gliosis 24 hours post RD. However, single or multiple
doses of BNN27 were not able to protect the overall survival of photoreceptors 7 days post
injury. Additionally, BNN27 did not induce the activation/phosphorylation of TrkAY490 in the
detached retina although the mRNA levels of the receptor were increased in the detached
photoreceptors. In NMDA-mediated retinal injury, BNN27 was able to reduce TUNEL+ cell
death only in the photoreceptors and not in the RGCs or the inner retina in any of the three
doses that we tested. Furthermore, it did not induce any changes in macrophage/microglia cell
infiltration or in NMDA-mediated retinal gliosis. Moreover, similarly to RD injury, BNN27
did not induce the activation/phosphorylation of TrkAY490 in the NMDA-mediated injured
retina although TrkA was downregulated following NMDA insult. Together, these findings,
do not demonstrate neuroprotective activity of BNN27 in experimentally-induced RD or
NMDA-mediated retinal excitotoxicity. Further studies are needed in order to elucidate the
paradox/contradiction of these results and the mechanism of action of BNN27 in these models
of acute retinal cell damage.
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Language |
English |
Subject |
NMDA excitotoxicity |
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NMDA διεγερσιτοξικότητα |
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Neurodegeneration |
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Neuroprotection |
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Retinal detachment |
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Αποκόλληση |
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Νευροεκφυλιστικά νοσήματα |
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Νευροπροστασία |
Issue date |
2019-03-27 |
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/0/3/8/metadata-dlib-1554718445-92927-16802.tkl
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Views |
1222 |