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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

Τσόκα, Αικατερίνη -Παυλίνα

Thesis advisor

Τσιλιμπάρης, Μιλτιάδης

Reviewer

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.

Language

English

Subject

NMDA excitotoxicity

NMDA διεγερσιτοξικότητα

Neurodegeneration

Neuroprotection

Retinal detachment

Αποκόλληση

Νευροεκφυλιστικά νοσήματα

Νευροπροστασία

Issue date