Neuroprotective effect of topically applied brimonidine tartrate 0.2% in endothelin-1-induced optic nerve ischaemia model.
BACKGROUND
To investigate the neuroprotective effects of topically applied brimonidine tartrate 0.2% (BMD), an alpha(2)-receptor agonist, on the retinal ganglion cell (RGC) layer and inner nuclear layer (INL) of rabbit retina in endothelin-1 (ET-1)-induced optic nerve (ON) ischaemia model.


METHODS
Osmotic minipumps were surgically implanted into one eye of 16 New Zealand Albino rabbits to deliver ET-1 at the constant rate of 0.5 microL/h for 2 weeks. Eyes were divided into four groups. ET-1 was given with (Group 3) and without topical BMD therapy (Group 1). Groups 2 and 4 were taken as controls. Rabbits were sacrificed at day 14. Morphological alterations, total cell number and proportion of cells undergoing apoptosis in INL and RGC layer were assessed by histopathological analysis to determine the survival of the cells of the INL and RGC layer.


RESULTS
Endothelin-1 led to severe reduction of cells in both the RGC layer and INL in Group 1 (P < 0.05). In Group 3, the total cell number and the proportion of cells undergoing apoptosis in the RGC layer were comparable with the control group (Group 4), whereas the former was found to be higher and the latter was found to be lower than those recorded for Group 1. However, the total cell number in the INL was found to be lower in Group 3 compared with that of Group 4, despite topical BMD therapy (P < 0.05).


CONCLUSIONS
Topically applied BMD seems to be neuroprotective and antiapoptotic in the ET-1-induced ON ischaemia model, especially for RGCs. BMD might be used as an adjuvant agent for its neuroprotective effects in hypoxic-ischaemic conditions such as diabetic retinopathy, normotensive glaucoma and other retinal vascular occlusive conditions which require further investigations.
Aktaş
Zeynep
Z
Department of Ophthalmology, Gazi Universit Medical Faculty, Ankara, Turkey. drzeynep2000@yahoo.com
Gürelik
Gökhan
G
Akyürek
Nalan
N
Onol
Merih
M
Hasanreisoğlu
Berati
B
D000287:Administration, Topical; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068438:Brimonidine Tartrate; D002452:Cell Count; D004195:Disease Models, Animal; D019332:Endothelin-1; D015918:Infusion Pumps, Implantable; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011810:Quinoxalines / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D018696:Neuroprotective Agents; D011810:Quinoxalines; D000068438:Brimonidine Tartrate