Abstract
Purpose::
Carbon monoxide-releasing molecules (CO-RMs) are a novel group of substances that are capable of modulating physiological functions via the liberation of CO. This study was undertaken to investigate the effects of CORM-3, a water-soluble CO-releasing agent, on a model of ocular hypertension in rabbits.
Methods::
New Zealand rabbits were used. All the animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Ocular hypertension was induced by injecting α-chymotrypsin in both eyes under local anaesthesia. Only rabbits with intraocular pressure (IOP) of 25 mmHg or more were used. The dose-response effect of CORM-3 on IOP was assessed by topical administration of the drug (0.001, 0.01, 0.1 and 1%) and subsequent IOP monitoring every 6 hours. In a separate set of experiments, animals were treated topically with an inactive form of the drug (iCORM-3) that is incapable of liberating CO.
Results::
CORM-3 caused a significant dose-dependent reduction of IOP in rabbits treated with α-chymotrypsin. No significant effect was observed on IOP and pupil diameter in normotensive eyes of control animals. Treatment with the inactive form of CORM-3 had no effect on IOP indicating that CO liberated by CORM-3 is responsible for the observed effect. These results support our previous findings on the effect of heme oxygenase-derived CO on IOP.
Conclusions::
Treatment with CORM-3 is associated with a reduction of IOP in a α-chymotrypsin model of ocular hypertension in rabbits. These findings suggest a direct involvement of CO in the regulation of ocular pressure likely through a modulation of aqueous humor dynamics.
Keywords: intraocular pressure • aqueous • nitric oxide