The role of endothelin-1 and its receptors in optic nerve head astrocyte proliferation.
OBJECTIVE
To characterise the influence of endothelin-1 (ET-1), a vasoactive peptide, and its receptors (endothelin B (ETB) and endothelin A (ETA)) on rat optic nerve head astrocyte (ONHA) proliferation.


METHODS
ONHAs were isolated from adult Brown Norway rats. ONHA specificity was determined with immunohistochemistry for: glial fibrillary acidic protein (GFAP); A2B5, a marker of type II astrocytes located outside the ONH; and myelin basic protein (MBP). ONHA proliferation was quantified following treatment with ET-1 (1x10(-6), 1x10(-7), 1x10(-9) or 1x10(-11) M) or vehicle for 24, 48 or 72 h. ETB and ETA antagonists were used to assess the role of each receptor in ONHA proliferation.


RESULTS
ONHA specificity was confirmed with positive labelling for GFAP, and negative labelling for A2B5 and MBP. ONHAs also expressed ETB and ETA. Cell percentages increased significantly beginning 48 h after ET-1 exposure with 1x10(-7) (20%) and 1x10(-9) M (15%). After 72 h, ONHA percentages increased significantly at all ET-1 concentrations (25%, 21%, 29%, 28% increases relative to vehicle, for 1x10(-6), 1x10(-7), 1x10(-9) and 1x10(-11) M, respectively). No significant proliferation occurred in the presence of either antagonist.


CONCLUSIONS
ONHAs proliferated following 48 h or more of exposure to ET-1. The proliferation required both ETB and ETA receptors.
Murphy
Jeremy A
JA
Department of Ophthalmology and Visual Sciences, Dalhousie University, 1276 South Park Street, 2W Victoria, Halifax, Nova Scotia, Canada B3H 2Y9.
Archibald
Michele L
ML
Chauhan
Balwantray C
BC
D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D049109:Cell Proliferation; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D009898:Optic Disk / Q000166:cytology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087220:BQ 610; C086539:BQ 788