Effect of ocular hypertension on retinal GABAergic activity
Section snippets
Introductory statement
Glaucoma, a chronic disease characterized by visual field loss, cupping of the optic nerve head, and irreversible loss of retinal ganglion cells (RGCs), is a leading cause of blindness worldwide. It is estimated that half of those affected may not be aware of their condition because symptoms may not occur during the early stages of the disease. When vision loss appears, considerable permanent damage has already occurred. Medications and surgery can help slow the progression of some forms of the
Reagents and drugs
GABA, l-glutamic acid, 3-mercaptopropionic acid, GABAse, pyridoxal phosphate and picrotoxin were obtained from Sigma Chemical Co. (St. Louis, MO, USA). [3H]-GABA, 1-[14C]-l-glutamic acid, [3H]-muscimol, and [35S]-t-butylbicyclophosphorothionate (TBPS) were purchased from New England Nuclear Corp. (Boston, MA, USA).
Animals and tissues
Male Wistar rats (average weight, 200 ± 40 g) were housed in a standard animal room with food and water ad libitum under controlled conditions of humidity and temperature (21 ± 2 °C), under
Effect of HA on IOP
Fig. 1 shows the average IOP of rats injected weekly with HA (in one eye) or vehicle in the other for 3 or 6 weeks. A significant increase of IOP was observed in eyes injected with HA as compared with the respective controls. No differences in IOP of vehicle-injected eyes were detected between these time-points or between non-injected and vehicle-injected eyes.
Effect of high IOP on the retinal GABAergic system
The effect of ocular hypertension on GABA steady state concentrations and GABA turnover rate is shown in Fig. 2. At 3 weeks of treatment
Discussion
For the first time, the foregoing results support a significant dysfunction of the retinal GABAergic system in rats exposed to experimentally elevated IOP. In particular, these results indicate that GABA steady state concentrations, GABA turnover rate, GAD activity, GABA transporters, and GABA receptors were susceptible to HA-induced ocular hypertension. In contrast to these results, Kielczewski et al. (2005) have recently shown that amacrine cells identified by GABA labeling were not affected
Acknowledgments
This research was supported by grants from The University of Buenos Aires, CONICET, and The Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), Argentina.
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