Suppression of corticosteroid-induced ocular hypertension in sheep by anecortave.
OBJECTIVE
To confirm the ocular hypotensive effects of anecortave acetate on an ovine model for steroid-induced ocular hypertension. Eyes of normal sheep exhibit a robust steroid-induced ocular hypertensive response. Recent observations in an uncontrolled, interventional case series indicated that anecortave elicited hypotensive effects when administered as a sub-Tenon depot in the eyes of a small sample of patients with glaucoma.


METHODS
Intraocular pressure (IOP) was monitored by Perkins applanation tonometry in 16 normal sheep receiving topically administered prednisolone acetate, 0.5%, in both eyes, 3 times daily, a protocol that doubled IOP within 12 days. Half of the sheep had received a unilateral sub-Tenon injection of anecortave in 1 eye prior to the initiation of the bilateral prednisolone instillations, while the 8 remaining sheep received the unilateral anecortave sub-Tenon depot after the IOP was maximally elevated by the prednisolone instillations.


RESULTS
In these 2 sets of experiments, the presence of the anecortave depot suppressed the steroid-induced IOP elevation and reverted the elevated IOP to baseline levels. Measurements of aqueous outflow facility indicated that eyes treated with prednisolone plus anecortave exhibited a 5.8-fold higher outflow facility than the fellow eyes solely exposed to prednisolone, indicating that anecortave prevented the increase in outflow resistance produced by the corticosteroid.


CONCLUSIONS
Elucidation of the mechanisms of action of anecortave in animal models may prove relevant to the design of novel interventions for the management of primary open-angle glaucoma.
Candia
Oscar A
OA
Departments of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA. oscar.candia@mssm.edu
Gerometta
Rosana
R
Millar
J Cameron
JC
Podos
Steven M
SM
D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D011239:Prednisolone / Q000031:analogs & derivatives / Q000633:toxicity; D011244:Pregnadienediols / Q000008:administration & dosage*; D012756:Sheep; D014065:Tonometry, Ocular
D020533:Angiogenesis Inhibitors; D005938:Glucocorticoids; D011244:Pregnadienediols; C009935:prednisolone acetate; D011239:Prednisolone; C418047:anecortave acetate