Effect of ocular hypertension on the retinal Gabaergic System

CECILIA MORENO; NURIA DE ZAVALÍA; INÉS KELLER SARMIENTO; RUTH ROSENSTEIN

Miami, USA

Congreso; Association for Research in Vision and Ophthalmology (ARVO); 2006

Association for Research in Vision and Ophthalmology (ARVO)

Purpose: GABA (ã-aminobutyric acid) and glutamate are major excitatory and inhibitory neurotransmitters in the vertebrate retina. Thus, the physiologic balance between these systems is a principle of key organization at retinal level. Although glutamate-induced excitotoxicity has been proposed to mediate the death of retinal ganglion cells in glaucoma, the retinal GABAergic activity was not previously examined in this retinal disease. The aim of the present work was to study the retinal GABAergic activity in eyes with ocular 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 6 weeks of treatment, GABA turnover rate was assessed through a radioreceptor assay. Glutamic acid decarboxylase (GAD) activity was measured using 1-[14C]-glutamate. In addition, GABA uptake and release were assessed with [3H]-GABA, whereas binding of t-butylbicyclophosphorothionate (TBPS) was analyzed using [35S]-TBPS. Results: At 3 weeks of treatment with HA a significant decrease of GABA turnover rate and GAD activity was observed. In addition, both glutamate- and high K+-induced GABA release significantly decreased, whereas GABA uptake increased in HA-treated eyes. TBPS binding significantly increased in eyes injected with HA for 3 weeks as compared with vehicle-injected eyes. Only the changes in TBPS binding and GABA uptake persisted at 6 weeks of treatment with HA. Conclusions: These results indicate a significant alteration of the retinal GABAergic activity in hypertensive eyes. Since these changes preceded both functional and histological alterations induced by ocular hypertension, these results support the involvement of GABA in glaucomatous neuropathy. Taken together with previous reports of an increase in retinal glutamate synaptic levels, these findings strongly support that glaucoma may greatly shift the excitation-inhibition balance and dramatically accelerate the overall neuronal activity within the retinal circuit.