We examined the expression of mGlu2/3
metabotropic glutamate receptors in the retina of the goldfish Carassius auratus. mGlu2/3 receptors were expressed in all
retinal layers internal to the photoreceptor layer, particularly in the outer and inner nuclear layers. Although the goldfish brain is able to tolerate prolonged periods of
anoxia, we examined whether
anoxia could induce
retinal damage. Three hours of
anoxia induced in the retina the development of apoptotic cell death, as assessed 48 h later by TUNEL staining. TUNEL-positive cells were particularly found in the inner and outer nuclear layers, and were also present in the
ganglion cell layer. Pharmacological activation of mGlu2/3 receptors by systemic injection of
LY379268 (0.5 mg/kg, i.p., 15 min before the onset of
anoxia) substantially protected retinas against
anoxia-induced cell death. In contrast, systemic injection of the mGlu2/3 receptor antagonist,
LY341495 (1 mg/kg, i.p., 15 min before the onset of
anoxia), significantly amplified cell death. Finally, as mGlu2/3 receptors are implicated in the control of extracellular
glutamate concentrations, we examined the stimulation of
glutamate release in isolated goldfish retinas. Depolarizing medium containing 30 mM KCl led to a significant increase in
glutamate release, which was substantially reduced by
LY379268. We conclude that activation of mGlu2/3 receptors may provide a major defensive mechanism against ischemic/anoxic
retinal damage.