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Identifier

000419922

Title

Μελέτη καινοτόμων θεραπειών για την αντιμετώπιση αμφιβληστροειδοπαθειών : αναστολείς NADPH οξειδασών

Alternative Title

Investigation of novel therapeutics for retinopathies

Author

Διονυσοπούλου, Σταυρούλα

Thesis advisor

Θερμού, Κυριακή

Reviewer

Τσιλιμπάρης, Μιλτιάδης
Χαραλαμπόπουλος, Ιωάννης

Abstract

NADPH oxidase inhibitors potentially contribute to the reduction of vasculopathy and inflammation in various models of retinopathies. However, less is known about the efficacy of these molecules against retinal neurodegeneration. The aim of this study was to evaluate the neuroprotective and anti-inflammatory actions of NADPH oxidase inhibitors, VAS2870 and ML171, in the in vivo model of AMPA excitotoxicity in the retina of Sprague-Dawley rats, using immunohistochemical studies. RT-PCR and immunohistochemical analysis, using an antibody against the NOX1 isoform, were also performed, to study the expression of the individual NOX isoforms in the control retina and in the in vivo model of AMPA excitotoxicity. The immunohistochemical study against brain nitric oxide synthase (bNOS) confirms the neuroprotective effect of both inhibitors on AMPA-induced loss of retinal amacrine cells. Furthermore, the results of the immunohistochemical studies, using antibodies against GFAP and Iba-1, demonstrate the anti-inflammatory activity of these agents. Both inhibitors decrease macroglial and microglial activation, respectively. RT-PCR results confirmed - qualitatively- the expression of the NOX1, NOX2 and NOX4 isoforms in control rat retina and in the model of AMPA excitotoxicity. Anti-NOX1 immunohistochemistry resulted in the observation that NOX1 is expressed in the Retinal Pigment Epithelium and in Retinal Ganglion Cells, while qualitatively, its expression was not modified due to AMPA induced excitotoxicity. In conclusion, NADPH oxidase inhibitors are potentially able to cope with the vascular, inflammatory and neuronal disorders that characterize ischemic retinopathies. Therefore, further investigation and evaluation of their efficacy will provide important data on their potential clinical use.

Language

Greek, English

Subject

Excitotoxicity

Neuroprotection

Διεγερτοτοξικότητα

Νευροπροστασία

Issue date

2018-12-05

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses