[doi: 10.5505/2017ichc.PP-16]

Comparison of the Neuroprotective Effects of Brimonidine Tartrate and Melatonin on Retinal Ganglion Cells

Deniz Marangoz1, Emine Elif Güzel Meydanlı2, Siğnem Eyüboğlu3, Aslı Gümüşel2, Ismail Seçkin2, Bayram Yılmaz3, Ilgaz Yalvaç1
1Department of Ophthalmology, Yeditepe University Faculty of Medicine, Istanbul, Turkey
2Department of Histology and Embryology, Istanbul Unıversity Cerrahpasa Faculty of Medicine, Istanbul, Turkey
3Department of Physiology, Yeditepe University Faculty of Medicine, Istanbul, Turkey

Glaucoma is a group of neurodegenerative conditions, which mainly involves the retinal ganglion cells (RGCs) and axons. It is the second leading cause of blindness worldwide. More than 60 million people are affected globally and it is estimated that more than 80 million people will be affected by 2020 and 10% of affected people will be suffering from bilateral blindness.
In this study we aimed to compare the neuroprotective effects of intraperitoneal injection of brimonidine tartrate (BRT) and melatonin (MEL) on retinal ganglion cells (RGCs) in a rat glaucoma model.
Thirty-six adult Wistar albino rats were allocated into six groups: Control (C), glaucoma (G), BRT, MEL, G+BRT, G+MEL. Glaucoma model was established by unilateral episcleral venous cauterization. At day 26, RGCs were retrogradely labeled with 3% Fluorogold, which was injected into the superior colliculus. Four days after intratectal injection, sacrification and enucleation were performed. TUNEL kit was used to label apoptotic RGCs and then apoptotic indices for each eye were calculated. Statistical analysis was performed by post hoc Holm-Sidak test after one-way ANOVA. Intraocular pressure (IOP) measurements were analyzed using Wilcoxon signed rank test.
Statistically significant IOP reductions were found in BRT, G+BRT and G+MEL groups. Intraperitoneal melatonin injections caused a significant IOP reduction only under glaucomatous conditions. Compared to G group, G+BRT group had lower apoptotic indices (p<0.05) and higher 3% Fluorogold-labeled cell counts (p<0.05). However, no statistical significance was found between G and G+MEL groups considering apoptotic index value and 3% Fluorogold-labeled cell counts (p<0.05). Brimonidine tartrate had a significant IOP reducing effect when applied systemically, in contrast to the reports in the literature. In addition, brimonidine tartrate appears to be neuroprotective on RGCs against glaucomatous injury. On the other hand, our research showed no neuroprotective effect of melatonin on retinal ganglion cells in glaucomatous neurodegeneration process.



Figure 1

TUNEL-labeled apoptotic RGCs are seen in brown color (black arrows). More apoptotic cells are seen in groups G and G+MEL than in G+BRT group. Groups shown are as follows: A) C group, B) BRT group, C) MEL group, D) G group, E) G+BRT group, F) G+MEL group. 40X magnification.


Figure 2

3% Fluorogold-labeled non-apoptotic cells are seen (white arrows). Nonapoptotic cells are very few in G and G+MEL groups when compared with the rest of the groups. Groups shown are as follows: A) C group, B) BRT group, C) MEL group, D) G group, E) G+BRT group F) G+MEL group. 20X magnification.