Both optic nerve (ON) transection and intraocular injection of N-methyl-D-aspartate (NMDA) are established lesion models to cause death of retinal ganglion cells (RGCs) in the adult rat. Excitotoxic effects via glutamate receptors resulting in secondary neuronal death are discussed as possible initiators in both types of RGC damage. We examined whether modulating glutamatergic transmission through metabotropic glutamate receptors rescues RGCs from lesion-induced degeneration in vivo. Unexpectedly, repeated intraocular injection of four different agonists/antagonists on the various subtypes of mGluRs did not decrease retinal damage in both lesion paradigms as revealed by measurement of visual performance and RGC survival. We conclude that activation/inactivation of retinal mGluRs does not play an important role for the initiation and execution of secondary RGC loss after ON transection and NMDA lesion in the adult rat.