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Identifier

000412965

Title

Μελέτη νέων θεραπευτικών μορίων για την αντιμετώπιση της διαβητικής αμφιβληστροειδοπάθειας

Alternative Title

Study of new therapeutic molecules for the treatment of diabetic retinopathy

Author

Φωθιαδάκη, Μυρτώ Ε.

Thesis advisor

Θερμού, Κυριακή

Reviewer

Γανωτάκης, Δημήτριος
Κατερινόπουλος, Χαράλαμπος

Abstract

Diabetic retinopathy (DR) is a microvascular disease characterized by neovascularization. More recent studies have suggested that DR is a neurodegenerative disease of the eye. While therapeutics for DR are available, they treat only the neovascular component of the disease. However, there is a great need for new therapies that target the neurodenerative component that leads to apoptotic cell death, a decrease of visual acuity and blindness. Neurosteroids, such as dehydroepiandrosterone (DHEA), have been shown to have antiapoptotic properties and to provide neuroprotection in the central nervous system and in models of DR. Unpublished studies in our laboratory have shown that DHEA and its analogue, BNN-27, protected the retina in the in vivo STZ model of DR, acting as a potential therapeutic molecule in the treatment of DR. The aim of the present study was to elucidate further the neuroprotective effects of BNN-27 in the DR model. In the present study, Sprague-Dawley adult rats were employed. The animals were placed in three groups [Control, diabetic (induced by streptozotocin), diabetic+BNN-27]. Two experimental paradigms were employed, namely paradigm A and B. In paradigm A, BNN-27 was administered intraperitoneally every two days, for the third and fourth week after the induction of diabetes. In experimental paradigm B, rats were treated with BNN-27 every two days for four weeks after the induction of diabetes. Immunohistochemical studies were performed using antibodies against retinal neurons, such as a) amacrine cells expressing the enzymes nitric oxide synthetase (bNOS) and tyrosine hydroxylase (TH), and b) the axons of ganglion cells (NFL). The immunoreactivity of all three markers was reduced in the diabetic retinas in a statistically significant manner compared to the retinas of the control group. The neurosteroid BNN-27 restored the immunoreactivity at the levels of the control group. TUNEL assay showed that the TUNEL+ cells were increased in the diabetic retina, yet BNN-27 had no effect. Immunohistochemical studies using an antibody against caspase-3, a more specific marker of apoptosis, also showed higher immunoreactivity in the diabetic retinas in agreement with the TUNEL results. However, BNN-27 was effective in reducing the caspase-3 induced apoptosis in a statistically significant manner compared to the diabetic group. This study provides important information regarding the neuroprotective effects of BNN-27, the synthetic analog of DHEA, in DR. The results suggest that this molecule may be useful as a potential therapeutic in DR that will improve the visual acuity of diabetic patients.

Language

Greek

Subject

Bnn-27

Neuroprotection

Νευροπροστασία

Issue date

2017-11-23

Collection

School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses

Type of Work--Post-graduate theses

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