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H. Oku, W. Goto, T. Okuno, M. Tsujimoto, T. Sugiyama, T. Ikeda; Effects of Poly(ADP-ribose) Polymerase (PARP) Inhibitor on NMDA-induced Retinal Injury . Invest. Ophthalmol. Vis. Sci. 2003;44(13):27.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Excessive activation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that is activated by DNA damage, leads to neuronal cell death through depletion of ATP. We evaluated whether inhibition of PARP has some neuroprotective effects on the NMDA-induced retinal injury in rabbits. Methods: Visually-evoked potentials (VEPs) were recorded at different times after an intravitreal injection of NMDA (200 and 2000 nmol) alone, or NMDA with 3-aminobenzamide (ABA, 200 nmol), a PARP inhibitor, or with MK-801 (200 nmol), an NMDA antagonist. The physiological changes were followed for 2 weeks after which the eyes were enuculeated and prepared for histological examinations. Results: ABA rescued primary cultured fetal rat retinal neurons from apoptotic and/or necrotic death induced by the brief exposure to NMDA (1.0 mM). Intravitreal injections of NMDA reduced the amplitudes of rabbit VEPs, and the number of retinal ganglion cells (RGCs) in a dose-dependent manner. No significant changes could be detected in the bright flash electroretinograms (ERGs). Simultaneous injection of MK-801 (200 nmol) significantly diminished the changes induced by intravitreal NMDA. ABA (200 nmol) also suppressed these changes, but its effects were less than those of MK-801. Conclusions: NMDA-induced retinal damage can be detected by VEPs. PARP inhibition has some neuroprotective effects on the NMDA-induced retinal damage, although the effects were less than those with MK-801.
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