Purpose: Under physiological conditions, levels of the excitatory neurotransmitter glutamate within the retina are regulated by retinal glutamate transporters to prevent toxic accumulation. Alterations in this glutamate buffering have been implicated in retinal ganglion cell (RGC) death. We quantified the changes in the level of glutamate transporter mRNA in a model of acute rat optic nerve injury.
Methods: Optic nerve damage was induced in one eye of 25 adult Wistar rats by partial optic nerve crush (ONC). Total mRNA levels of the retinal glutamate transporter GLT-1 (EAAT-2) were determined by quantitative real-time PCR. GLT-1 mRNA levels were measured 1, 3, 7, 14, and 28 days following optic nerve injury. Additionally, control values were obtained from the retinas of five control rats (sham-crush).
Results: In the very early phase (1 day post-ONC), a 3.9 fold increase in levels of GLT-1 mRNA was observed in the ONC retinae compared with control eyes. This was followed by a rapid decrease towards control levels at day 3 post-ONC. GLT-1 mRNA levels remained up to 14 days post-crush. However, in the late phase post-ONC (day 28), the level of GLT-1 mRNA increased again, but still remained not significant to control levels.
Conclusions: Changes in GLT-1 mRNA expression following axonal trauma of RGCs can lead to an imbalance of glutamate homeostasis. This may cause local accumulation of toxic concentrations of the neurotransmitter glutamate and further irreversible excitotoxic damage of RGCs.