June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Neuroprotective Effect of DHEA-derivative BNN27 against N-Methyl-D-Aspartate-induced Retinal Excitotoxicity in Mice
Author Affiliations & Notes
  • Pavlina Tsoka
    Neurology & Sensory Organs, Eye Research Lab, University of Crete, School of Medicine, Heraklion, Crete, Greece
    Massachusetts Eye and Ear Infirmary, Angiogenesis Lab, Harvard Medical School, Boston, MA
  • Ioannis Charalampopoulos
    Pharmacology, University of Crete, School of Medicine, Heraklion, Crete, Greece
  • Achilleas Gravanis
    Pharmacology, University of Crete, School of Medicine, Heraklion, Crete, Greece
  • Demetrios Vavvas
    Massachusetts Eye and Ear Infirmary, Angiogenesis Lab, Harvard Medical School, Boston, MA
  • Miltiadis Tsilimbaris
    Neurology & Sensory Organs, Eye Research Lab, University of Crete, School of Medicine, Heraklion, Crete, Greece
    Eye Clinic, University Hospital of Heraklion, Heraklion, Crete, Greece
  • Footnotes
    Commercial Relationships Pavlina Tsoka, None; Ioannis Charalampopoulos, Company: Bionature E.A. Ltd, PCT (International Publication Number): WO 2008/155534 A2 (P); Achilleas Gravanis, Bionature EA Ltd (P); Demetrios Vavvas, MEEI (P), Kala pharmaceuticals (C), Roche (C), Genentech (C); Miltiadis Tsilimbaris, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3250. doi:
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      Pavlina Tsoka, Ioannis Charalampopoulos, Achilleas Gravanis, Demetrios Vavvas, Miltiadis Tsilimbaris; Neuroprotective Effect of DHEA-derivative BNN27 against N-Methyl-D-Aspartate-induced Retinal Excitotoxicity in Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3250.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To investigate the neuroprotective role of a novel synthetic analogue (BNN27) of Dehydroepiandrosterone in an experimental model of N-methyl-D-aspartate induced (NMDA) retinal excitotoxicity in mice after intraperitoneal submission. BNN27 passes through the blood-brain barrier and interact with nerve growth factor (NGF) receptors, TrkA and p75.

Methods: Six to eight week old C57BL/6 mice were used. NMDA 100mg/ml (2 μl) was injected intravitreal with a 33g Hamilton syringe in deeply anesthetized animals. Animals were treated daily with IP injections of BNN27 (40mg/kg or 100mg/kg) or ethanol vehicle. Mice were sacrificed 24 and 72 hours later. TUNEL staining was performed in order to evaluate cellular death. Six animals per group and time point were evaluated.

Results: NMDA induced apoptotic cell death was similar 24 and 72 hours after intravitreal administration (36±4 and 42±6 TUNEL positive cells/section respectively. (mean ± SD). Treatment resulted in a dose dependent reduction in TUNEL positive cells in the ganglion cell layer both in 24 and 72 hours after NMDA induced retinal excitotoxicity. Treatment with 40mg/kg of BNN27 reduced TUNEL positive cells to 22±4 and 25±4 TUNEL positive cells/section, while BNN27 at 100mg/kg significantly reduced TUNEL positive cells to 13±2 cells/section and 8±2 cells/section at 24 and 72 hours after NMDA intravitreal injection respectively.

Conclusions: BNN27 appears to exert anti-apoptotic effects in NMDA retinal excitotoxicity induced apoptosis, possibly through its interaction with NGF receptors, representing a potential lead molecule to develop new neuroprotective agents for retina degeneration.

Keywords: 615 neuroprotection • 426 apoptosis/cell death • 517 excitatory amino acid receptors  
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