Hemin, an inducer of heme oxygenase-1, lowers intraocular pressure in rabbits.
OBJECTIVE
Carbon monoxide (CO) generated from heme may induce vasodilation and exert cyto-protective properties in the eye. This study was undertaken to investigate the effects of hemin, a potent inducer of heme oxygenase-1 (HO-1), on models of ocular hypertension in rabbits.


METHODS
Ocular hypertension was induced by injecting alpha-chymotrypsin in both eyes under local anesthesia. Only rabbits with an intraocular pressure (IOP) of 25 mmHg or more were used. The dose-response study of the hemin effect on IOP was made by an intravenous injection of the drug (50, 75, and 100 mg/kg) and subsequent IOP monitoring every 6 h. A separate set of animals was pretreated with the HO-1 inhibitor, zinc protoporphyrin-IX (ZnPP-IX, 0.1 mg/kg) 6 h before the vehicle or a 100-mg/kg hemin injection. Ocular hypertension was also obtained by the subconjunctival injection of betamethasone 21-phosphate disodium (4 mg/mL) in both eyes every week for 4 weeks. Only animals with an IOP of 30 mmHg or more were included in the experimental session. A group of these animals was pretreated with ZnPP-IX (0.1 mg/kg) 6 h before the vehicle or a 100-mg/kg hemin injection, and IOP was assessed every 6 hours.


RESULTS
Hemin caused a significant dose-related reduction of IOP in rabbits with alpha-chymotrypsin-induced ocular hypertension. No significant effect was observed in the normotensive eyes of the control animals or on pupil diameter. Pretreatment with the HO-1 inhibitor, ZnPP-IX, abolished the decrease of IOP that was induced by the maximum dose of hemin (100 mg/kg). A similar reduction in IOP was observed in those rabbits with betamethasone-induced ocular hypertension who were treated with 100 mg/kg of hemin. Furthermore, pretreatment with ZnPP-IX prevented the hemin effect on IOP.


CONCLUSIONS
The induction of HO-1 by hemin leads to a reduction of IOP in the alpha-chymotrypsin and betamethasone models of ocular hypertension. These results suggest an involvement of CO in the regulation of ocular pressure in rabbits.
Privitera
Maria G
MG
Department of Experimental and Clinical Pharmacology, University of Catania Medical School, Catania, Italy.
Potenza
Marta
M
Bucolo
Claudio
C
Leggio
Gian M
GM
Drago
Filippo
F
D000704:Analysis of Variance; D000818:Animals; D001623:Betamethasone / Q000031:analogs & derivatives; D002918:Chymotrypsin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism*; D006427:Hemin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011524:Protoporphyrins; D011817:Rabbits; D011897:Random Allocation
D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006427:Hemin; C028994:betamethasone sodium phosphate; D001623:Betamethasone; D051547:Heme Oxygenase-1; D002918:Chymotrypsin; C117608:alpha-chymotrypsin