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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)
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.
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