May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Neuroprotective Effect of Lens Epithelium-Derived Growth Factor (LEDGF) on N-Methyl-D-Aspartate-Induced Cell Death in Rat Retina
Author Affiliations & Notes
  • Y. Inomata
    Ophtalmology, Kumamoto univ. School of Med., Kumamoto, Japan
  • A. Hirata
    Ophtalmology, Kumamoto univ. School of Med., Kumamoto, Japan
  • T. Koga
    Ophtalmology, Kumamoto univ. School of Med., Kumamoto, Japan
  • T. Shinohara
    Ophtalmology, University of Nebraska Medical Center, Omaha, NE, United States
  • D.P. Shingh
    Ophtalmology, University of Nebraska Medical Center, Omaha, NE, United States
  • A. Kimura
    Ophtalmology, University of Nebraska Medical Center, Omaha, NE, United States
  • H. Tanihara
    Ophtalmology, University of Nebraska Medical Center, Omaha, NE, United States
  • Footnotes
    Commercial Relationships  Y. Inomata, None; A. Hirata, None; T. Koga, None; T. Shinohara, None; D.P. Shingh, None; A. Kimura, None; H. Tanihara, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 5206. doi:
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      Y. Inomata, A. Hirata, T. Koga, T. Shinohara, D.P. Shingh, A. Kimura, H. Tanihara; Neuroprotective Effect of Lens Epithelium-Derived Growth Factor (LEDGF) on N-Methyl-D-Aspartate-Induced Cell Death in Rat Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5206.

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

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Abstract

Abstract: : Purpose: To determine if lens epithelium-derived growth factor (LEDGF) has a neuroprotective effect against N-methyl-D-aspartate (NMDA)-induced cell death in retina. Methods: 6-week-old Sprague-Dawley (SD) rats received an intravitreal injection of LEDGF fused with glutathione-S-transferase (GST-LEDGF). Fellow eyes received vehicle as control. 7, 4 and 2 days after injection, same time, and 1day before injection of GST-LEDGF, eyes of rats were administered with NMDA (total amount of 20nmol) into the vitreous cavity. Each eye was enucleated, then transverse sections were subjected to morphometric analysis. Retrograde labeling with a fluorescent tracer (fluoro-Gold) was applied for counting survived retinal ganglion cells (RGCs) 4days after NMDA injection. Retinal damage was assessed by TUNEL-method 18 hours after NMDA injection. Western blotting analysis was perfomed for examination of heat shock protein 25 (Hsp25) and aB-crystallin in GST-LEDGF injected retina. Results: Pretreatment with GST-LEDGF 4 and 2 days before administration of NMDA provided a significant neuroprotective effect against NMDA-induced retinal damage. Retrograde labeling experiments revealed pretreatment with GST-LEDGF at 2days before NMDA injection induced neuroprotective effect of RGCs. In TUNEL method, it revealed that pretreatment with GST-LEDGF prevents NMDA induced apoptosis. Western blotting studies demonstrated upregulation of Hsp25 andaB-crystallin expression in retina of LEDGF injection from 24 to 48 hours. Conclusions: Present studies suggest that GST-LEDGF provides neuroprotective effects on RGCs against NMDA-induced retinal damage. The increased expression of Hsp25 and aB-crystallin may play a crucial role of this effects.

Keywords: neuroprotection • growth factors/growth factor receptors • retina: proximal(bipolar, amacrine, and gangli 
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