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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)2429-2436
Number of pages8
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume257
Issue number11
DOIs
StatePublished - 1 Nov 2019

Keywords

  • ERK1/2 kinases
  • Nerve growth factor
  • Neurodegeneration
  • Neuroprotection
  • Retinal disease
  • TrkA receptor

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