The aim of the present studies was to determine whether
nicotinamide is effective in blunting the negative influence of
ischemia/reperfusion to the rat retina in situ and of light to transformed retinal ganglion cells (RGC-5 cells) in culture.
Ischemia was delivered to the retina of one eye of rats by raising the intraocular pressure.
Nicotinamide was administered intraperitoneally just before
ischemia and into the vitreous immediately after the insult. Electroretinograms (ERGs) of both eyes were recorded before and 5 days after
ischemia. Seven days after
ischemia, retinas were analysed for the localization of various
antigens.
Retinal and optic nerve extracts were also prepared for analysis of specific
proteins and mRNAs. Also, RGC-5 cells in culture were given a light insult (1000 lux, 48 and 96 h) and evidence for reduced viability and apoptosis determined by a variety of procedures.
Nicotinamide was added to some cultures to see whether it reversed the negative effect of light.
Ischemia/reperfusion to the retina affected the localization of Thy-1,
neuronal nitric oxide synthase (NOS) and
choline acetyltransferase (ChAT), the a- and b-wave amplitudes of the ERG, the content of various
retinal and optic nerve
proteins and mRNAs. Significantly,
nicotinamide statistically blunted many of the effects induced by
ischemia/reperfusion which included the activation of
poly-ADP-ribose polymerase (PARP). Light-induced apoptosis of RGC-5 cells in culture was attenuated by
nicotinamide and the
PARP inhibitor NU1025. The presented data show that
nicotinamide attenuates injury to the retina and RGC-5 cells in culture caused by
ischemia/reperfusion and by light, respectively. Evidence is provided to suggest that
nicotinamide acts as a
PARP inhibitor and possibly an
antioxidant.