Effect of Ocular Hypertension on the Retinal Glutamate/Glutamine Cycle Activity

Abstract

Abstract: : Purpose: 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). Methods: 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 using [³H]–glutamate or [³H]–glutamine as radioligands, respectively. In addition, glutamine synthetase (GS) activity was assessed by a spectrophotometric assay, whereas glutaminase activity was measured through the conversion of [³H]–glutamine to [³H]–glutamate. Results: At 3 weeks of treatment with HA a significant decrease of glutamate uptake and GS activity was observed (P< 0.01). Glutamine uptake and release, as well as glutaminase activity significantly increased (P< 0.01) in eyes injected with HA for 3 weeks as compared with vehicle–injected eyes, whereas [³H]–glutamate release did not change in hypertensive eyes. Only the changes in GS activity persisted at 10 weeks of treatment with HA. Conclusions: These results indicate a significant alteration of 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.

Keywords: excitatory neurotransmitters • neurotransmitters/neurotransmitter systems • receptors: pharmacology/physiology