Impact Factor 3.648 | CiteScore 3.99
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01089

Carbamazepine alleviates retinal and optic nerve neural degeneration in diabetic mice via nerve growth factor-induced PI3K/Akt/mTOR activation

Nehal Elsherbiny M. Elsherbiny1,  Yousra Abdel-mottaleb2*,  Amany Y. Elkazaz3, 4, Hoda Atef5,  Rehab M. Lashine6, Amal M. Youssef7, Wessam Ezzat8,  Sabah H. El-Ghaiesh9, Rabie E. Elshaer10, Mohammed El-Shafey El-Shafey11 and  Sawsan A. Zaitone6
  • 1Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Egypt
  • 2Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Industries, Future University in Egypt, Egypt
  • 3Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Egypt
  • 4Faculty of Medicine, Port Said University, Egypt
  • 5Department of Histology and Cytology, Faculty of Medicine, Mansoura University, Egypt
  • 6Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Egypt
  • 7Department of Physiology, Faculty of Medicine, Suez Canal University, Egypt
  • 8Department of Physiology, Faculty of Medicine, Ain-Shams University, Egypt
  • 9Faculty of Pharmacy, Tanta University, Egypt
  • 10Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Egypt
  • 11Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt

Abstract

Aim: Diabetic retinopathy causes loss of vision in adults at working-age. Few therapeutic options are available for treatment of diabetic retinopathy. Carbamazepine (CARB), a widely used antiepileptic drug, was recently accounted for its neuroprotective effect. Nerve growth factor (NGF) activates various cascades among which, PI3K/Akt/mTOR pathway has a vital action in NGF-mediated neuronal differentiation and survival. This study evaluated the effect of CARB in the treatment of diabetic retina and unveiled some of the underlying molecular mechanisms. Main methods: Alloxan diabetes model was induced in 36 albino well-acclimatized mice. After establishment of the diabetic model in 9 weeks, mice were assigned to treatment groups: 1) saline, 2) alloxan-diabetic, 3 & 4) alloxan+CARB (25 or 50 mg per kg p.o) for 4 weeks. After completion of the therapeutic period, mice were sacrificed and eyeballs were enucleated. Retinal levels of NGF and PI3K/Akt were assessed using real-time polymerase chain reaction. Further, phospho-TrKA and total TrKA were measured by Western blot analysis. Key findings: Histopathological examination demonstrated that CARB attenuated vacuolization and restored normal thickness and organization of retinal cell layers. In addition, CARB increased pTrKA/TrKA ratio and ameliorated diabetes-induced reduction of NGF mRNA and immunostaining in retina. Additionally, it augmented the mRNA expression of PI3K, and Akt as well as the protein level of the phosphorylated PI3/Akt/mTOR. Significance: Results highlighted for the first time the neuronal protective effect for CARB in diabetic retina which is mediated, at least partly, by activation of NGF/PI3K/Akt/mTOR pathway.

Keywords: NGF (Nerve Growth Factor), PI3K/Akt/mTOR pathway, Neuroprotection, Carbamazepine, Diabetic Retinopathty, Apoptosis

Received: 29 Jun 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Elsherbiny, Abdel-mottaleb, Elkazaz, Atef, Lashine, Youssef, Ezzat, El-Ghaiesh, Elshaer, El-Shafey and Zaitone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yousra Abdel-mottaleb, Future University in Egypt, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Industries, New Cairo, Egypt, yabdelmottaleb@hotmail.com