Abstract
Purpose::
We have previously reported (Nucci C. ARVO 2006) that topical treatment with Coenzyme Q10 and Vitamin E reduces retinal ganglion cell death evoked by high intraocular pressure (IOP)-induced ischemia. To gain more insight in the neuroprotective profile of Coenzyme Q10 we tested the hypothesis that it may modulate the intraretinal levels of glutamate.
Methods::
Anaesthetized (urethane 1500 mg/kg i.p.) Sprague-Dawley rats, bearing a retinal microdialysis probe to measure extracellular glutamate (Richards et al.,Neuropharmacology 2000), have been used. For test studies, animals received (30 min before ischemia) intraretinal administration (via the microdialysis probe; 2 µl/min rate, 5 min duration of treatment in all instance) of 1) CoQ10 (solution of CoQ10 0.1% + vitamin E 0.5%), 2) vitamin E (Vit-E, 0.5%) or 3) vehicle (saline + EDTA 0.1%).
Results::
Microdialysis studies show that high IOP-induced ischemia increases intraretinal glutamate levels sensitive to the reversal of CoQ10. The increase in glutamate (199.3± 43.7% vs. pre-ischemia levels set to 100%; pre-ischemia glutamate levels= 0.307±0.044 µM, n=6) peaks at 130 min after reperfusion. Intraretinal administration, via the probe of CoQ10 (n=3, administered 30 min before ischemia), significantly reduces glutamate peak increase (26.06±12.1% vs 130 min reperfusion levels, p<0.001) whereas vehicle or Vit-E were without significant effect [141.4±56.5, (n=3) and 123.7±31.6 (n=5), respectively].
Conclusions::
The present data demonstrate that Vit-E and CoQ10 are able to reduce the increase of glutamate levels induced in the retina by high IOP though CoQ10 only achieves statistical significance. This effect may contribute to the neuroprotection afforded by topical application of CoenzymeQ10 and Vit-E in rats undergoing ischemia/reperfusion.
Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • neuroprotection • neurotransmitters/neurotransmitter systems