Retina and optic nerve diseases are one of the major causes of irreversible blindness worldwide, with increasing prevalence associated with aging of the population. Since there is no fully reliable and successful method for culturing retinal neurons (i.e., retinal ganglion cells, RGC) and furthermore, in vivo studies are relatively costly and time consuming, the ex vivo organotypic retinal culture could be a competitive and highly efficient method for initial drug toxicity screening. Neuroprotection and neuroregeneration are topics of a growing number of studies regarding eye diseases. Ocular pathologies result in neurodegeneration primary or secondary involving RGCs. Metallothioneins (MTs) are low molecular weight cysteine rich proteins. It is suggested that MTs, especially the isoform 2, are important neuroprotective substances for cerebral ischemia and retinal diseases. MT2 as a secondary antioxidant cooperates with reduced glutathione in the cellular protective system against oxidative stress. Additionally, it has been demonstrated that MT treatment can alleviate neurodegeneration of RGC in retinal explants exposed to toxic concentration of gentamycin. This protective effect, linked most probably to antioxidant activity, is associated with delayed increase of HuR protein content in retinal explants, which could be considered as a marker of delayed cells stress response.