PurposeWe aimed to compare the neuroprotective effects of brimonidine tartrate (BRT) and melatonin (MEL) on retinal ganglion cells (RGCs) in a rat glaucoma model.MethodsThirty-six adult Wistar albino rats were allocated into six groups: control (C), glaucoma (G), BRT, MEL, G+BRT and G+MEL. After establishing the glaucoma model, intraocular pressure (IOP) of all animals measured at day 4 and day 30 was compared statistically with day 0 and day 4, respectively. Prior to sacrification at day 30 for histological evaluation and TUNEL analysis, retrograde labeling of non-apoptotic RGCs with 3% Fluorogold was performed and RGCs were evaluated under fluorescein microscope.ResultsIOP measurements at day 4 were significantly higher than basal measurements in all glaucoma groups. BRT alone induced a time-dependent decrease in IOP (p<0.05), while MEL alone failed to reduce IOP. However, both BRT and MEL reduced IOP in the presence of glaucoma at day 30 (p<0.05). BRT treatment significantly reversed the reduced non-apoptotic RGC counts (p<0.01) and increased TUNEL-positive RGCs (p<0.001) to control group levels in the presence of glaucoma. However, no statistical significance was found between groups G and G+MEL considering 3% Fluorogold-labeled cell counts and apoptotic index values.ConclusionOur study revealed that systemic administration of BRT also has an IOP reducing effect. MEL has no neuroprotective effect on RGCs; on the other hand, BRT acts as a neuroprotective agent against glaucomatous injury, when applied systemically.