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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-11-2019 | Diabetic Retinopathy | Basic Science

Effect of topical administration of the microneurotrophin BNN27 in the diabetic rat retina

Authors: Ruth Ibán-Arias, Silvia Lisa, Smaragda Poulaki, Niki Mastrodimou, Ioannis Charalampopoulos, Achille Gravanis, Kyriaki Thermos

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 11/2019

Abstract

Purpose

Diabetic retinopathy (DR) is a complex eye disease associated with diabetes mellitus. It is characterized by three pathophysiological components, namely microangiopathy, neurodegeneration, and inflammation. We recently reported that intraperitoneal administration of BNN27, a novel neurosteroidal microneurotrophin, reversed the diabetes-induced neurodegeneration and inflammation in rats treated with streptozotocin (STZ), by activating the NGF TrkA and p75 receptors. The aim of the present study was to investigate the efficacy of BNN27 to protect retinal neurons when applied topically as eye drops in the same model.

Methods

The STZ rat model of DR was employed. BNN27 was administered as eye drops to diabetic Sprague-Dawley rats for 7 days, 4 weeks post-STZ (70 mg/kg) injection. Immunohistochemistry and western blot analyses were employed to examine the viability of retinal neurons in control, diabetic, and diabetic-treated animals and the involvement of the TrkA receptor and its downstream signaling ERK1/2 kinases, respectively.

Results

BNN27 reversed the STZ-induced attenuation of the immunoreactive brain nitric oxide synthetase (bNOS)- and tyrosine hydroxylase (TH)-expressing amacrine cells and neurofilament (NFL)-expressing ganglion cell axons in a dose-dependent manner. In addition, BNN27 activated/phosphorylated the TrkA receptor and its downstream prosurvival signaling pathway, ERK1/2 kinases.

Conclusions

The results of this study provide solid evidence regarding the efficacy of BNN27 as a neuroprotectant to the diabetic retina when administered topically, and suggest that its pharmacodynamic and pharmacokinetic profiles render it a putative therapeutic for diabetic retinopathy.

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Title: Effect of topical administration of the microneurotrophin BNN27 in the diabetic rat retina
Authors: Ruth Ibán-Arias
Silvia Lisa
Smaragda Poulaki
Niki Mastrodimou
Ioannis Charalampopoulos
Achille Gravanis
Kyriaki Thermos
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Diabetic Retinopathy
Diabetic Retinopathy
Retinal Diseases
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 11/2019
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-019-04460-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of topical administration of the microneurotrophin BNN27 in the diabetic rat retina

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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