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Abstract #13317 Published in IGR 8-1
Effect of glaucoma on the retinal glutamate/glutamine cycle activity
Moreno MC; Sande P; Marcos HA; de Zavalia N; Keller Sarmiento MI; Rosenstein REFASEB Journal 2005; 19: 1161-1162
Glutamate-induced excitotoxicity has been proposed to mediate the death of retinal ganglion cells in glaucoma. The metabolic dependence of glutamatergic neurons upon glia via the glutamate/glutamine cycle to provide the precursor for neurotransmitter glutamate is well established. Thus, the aim of the present work was to study the retinal glutamate/glutamine activity in eyes with hypertension induced by intracameral injections of hyaluronic acid (HA). For this purpose, weekly injections of HA were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with saline solution. At 3 or 10 weeks of treatment, glutamate and glutamine uptake and release were assessed using3 H-glutamate and3 H-glutamine as radioligands, respectively. In addition, glutamine synthetase activity was assessed by a spectrophotometric assay, whereas glutaminase activity was measured through the conversion of3 H-glutamine to3 H-glutamate. At 3 weeks of treatment with HA, a significant decrease (P < 0.01) in glutamate uptake and glutamine synthetase activity was observed. Glutamine uptake and release, as well as glutaminase activity, were significantly increased (P < 0.01) in eyes injected with HA for 3 weeks compared with vehicle-injected eyes, whereas3 H-glutamate release did not change in hypertensive eyes. Only the changes in glutamine synthetase activity persisted at 10 weeks of treatment with HA. These results indicate a significant alteration in the retinal glutamate/glutamine cycle activity in hypertensive eyes. Since these changes preceded both functional and histological alterations induced by ocular hypertension, these results support the involvement of glutamate in glaucomatous neuropathy.
Dr. M.C. Moreno, Laboratorio de Neuroquimica Retiniana y Oftalmologia Experimental, Departamento de Bioquimica Humana, Facultad de Medicina, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models