title: Pharmacological activation of mGlu2/3 metabotropic glutamate receptors protects retinal neurons against anoxic damage in the goldfish Carassius auratus.
abstract: 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.
authors.affiliation: Department of Biology, University of Bologna, 40126 Bologna, Italy.
authors.forename: Alina
authors.initials: A
authors.lastname: Beraudi
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.forename: Liborio
authors.initials: L
authors.lastname: Rampello
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poli
mesh_terms: D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006054:Goldfish; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D023421:Models, Animal; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013687:Telencephalon / Q000737:chemistry; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid