TY - JOUR
T1 - Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes
AU - Wang, Rong Fang
AU - Podos, Steven M.
AU - Serle, Janet B.
AU - Baltatu, Ovidiu C.
N1 - Funding Information:
Supported by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY and Speedel Experimenta Ltd.3, Basel, Switzerland .
PY - 2012/1
Y1 - 2012/1
N2 - The effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) was evaluated in the eyes of monkeys with laser induced unilateral glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes with 3 concentrations of SPP 635, 0.2%, 0.3% and 0.4%. IOP was measured hourly for 6h on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50μl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50μl drop (25μl×2) of SPP 635, 0.2%, 0.3% or 0.4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p<0.05) reduced IOP. The maximum reduction in IOP occurred 3 or 4h after morning dosing and was 4.3±0.8 (mean±SEM) mmHg (14%) for 0.2% SPP 635, 5.3±1.0mmHg, (19%) for 0.3% SPP 635, and 8.0±1.3mmHg (25%) for 0.4% SPP 635. The longest duration of IOP reduction was for 6h with 0.2% or 0.3% SPP 635, and was for at least 18h with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p<0.05) and longer duration of IOP reduction (18 vs. 6h). Mild conjunctival discharge appeared in 2 of 8 eyes, and hyperemia appeared in 2 eyes with the 0.3% and 0.4% concentrations on treatment days 3 and 5. Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkeys in a dose-dependent manner. Renin inhibitors, are a novel class of compounds which may have potential for the treatment of glaucoma.
AB - The effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) was evaluated in the eyes of monkeys with laser induced unilateral glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes with 3 concentrations of SPP 635, 0.2%, 0.3% and 0.4%. IOP was measured hourly for 6h on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50μl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50μl drop (25μl×2) of SPP 635, 0.2%, 0.3% or 0.4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p<0.05) reduced IOP. The maximum reduction in IOP occurred 3 or 4h after morning dosing and was 4.3±0.8 (mean±SEM) mmHg (14%) for 0.2% SPP 635, 5.3±1.0mmHg, (19%) for 0.3% SPP 635, and 8.0±1.3mmHg (25%) for 0.4% SPP 635. The longest duration of IOP reduction was for 6h with 0.2% or 0.3% SPP 635, and was for at least 18h with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p<0.05) and longer duration of IOP reduction (18 vs. 6h). Mild conjunctival discharge appeared in 2 of 8 eyes, and hyperemia appeared in 2 eyes with the 0.3% and 0.4% concentrations on treatment days 3 and 5. Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkeys in a dose-dependent manner. Renin inhibitors, are a novel class of compounds which may have potential for the treatment of glaucoma.
KW - Glaucoma monkey
KW - Intraocular pressure
KW - Renin inhibitor
KW - Renin-angiotensin system
KW - SPP 635
UR - http://www.scopus.com/inward/record.url?scp=84855831401&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2011.11.019
DO - 10.1016/j.exer.2011.11.019
M3 - Article
C2 - 22173206
AN - SCOPUS:84855831401
SN - 0014-4835
VL - 94
SP - 146
EP - 149
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 1
ER -