AUTHOR=Elsherbiny Nehal M. , Abdel-Mottaleb Yousra , Elkazaz Amany Y. , Atef Hoda , Lashine Rehab M. , Youssef Amal M. , Ezzat Wessam , El-Ghaiesh Sabah H. , Elshaer Rabie E. , El-Shafey Mohamed , Zaitone Sawsan A. 

TITLE=Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 13 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.01089

DOI=10.3389/fnins.2019.01089

ISSN=1662-453X

ABSTRACT= 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.