Pharmacological Study on the Effects of Some Ocular Hypotensive Drugs on Aqueous Humor Formation in the Arterially Perfused Enucleated Rabbit Eye

Abstract

The effects of pilocarpine, isoproterenol, epinephrine, timolol, acetazolamide, ouabain, and dinitrophenol on aqueous humor production were investigated in enucleated rabbit eye. The metabolic inhibitors ouabain and dinitrophenol at a concentration of 10^––⁵M produced a 50% inhibition in aqueous humor formation. Acetazolamide at the same concentration was without effect, but at 10^––4M concentration lowered aqueous production by 40%. The autonomic drugs epinephrine and isoproteranol at a concentration of 10 µg/ml medium reduced aqueous humor formation by 64 and 52% respectively. Timolol, even at a concentration of 0.05 µg/ml, suppressed aqueous humor formation by approximately 30%. Pilocarpine on the other hand was ineffective. Except for pilocarpine, these responses are similar to those reported to occur in the cat both in vivo and in vitro.

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

“…Acetazolamide reduces the rate of blood-to-aqueous 14 C-labelled bicarbonate movement (Zimmerman et al, 1976). This is in accordance with their ability to reduce AH formation in dogs (Maren, 1976) and rabbits (Caprioli and Sears, 1984;Kodama et al, 1985), species in which the CE concentrates bicarbonate from blood to aqueous and the AH is bicarbonate-rich. Curiously, however, the CAIs reduce aqueous formation equally efficiently in eyes where the concentration of bicarbonate in plasma and aqueous is similar in human (Dailey et al, 1982;Toris et al, 2004), monkey (Wang et al, 1991), bovine (Shahidullah et al, 2003) and pig (Shahidullah et al, 2009).…”

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

“…Acetazolamide reduces the rate of blood-to-aqueous 14 C-labelled bicarbonate movement (Zimmerman et al, 1976). This is in accordance with their ability to reduce AH formation in dogs (Maren, 1976) and rabbits (Caprioli and Sears, 1984;Kodama et al, 1985), species in which the CE concentrates bicarbonate from blood to aqueous and the AH is bicarbonate-rich. Curiously, however, the CAIs reduce aqueous formation equally efficiently in eyes where the concentration of bicarbonate in plasma and aqueous is similar in human (Dailey et al, 1982;Toris et al, 2004), monkey (Wang et al, 1991), bovine (Shahidullah et al, 2003) and pig (Shahidullah et al, 2009).…”

Nonpigmented Ciliary Epithelial Cells Respond to Acetazolamide by a Soluble Adenylyl Cyclase Mechanism

“…[6][7][8][9] Carbonic anhydrase inhibitors target carbonic anhydrases with high selectivity, preventing catalysis of the reversible hydration of carbon dioxide to generate bicarbonate ions and protons. They reduce aqueous humor formation and intraocular pressure in all species that have been tested, including bovines, 10 rabbits, 11,12 dogs, 13 monkeys, 14 and humans, 15 as well as in the intact porcine eye. 16 Our past studies on ciliary epithelium of the porcine eye demonstrated robust expression of both membrane-bound (CAIV) and cytoplasmic (CAII) carbonic anhydrase in the NPE.…”

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

“…Acetazolamide reduces the rate of blood-to-aqueous 14 C-labelled bicarbonate movement (Zimmerman et al, 1976). This is in accordance with their ability to reduce AH formation in dogs (Maren, 1976) and rabbits (Caprioli and Sears, 1984;Kodama et al, 1985), species in which the CE concentrates bicarbonate from blood to aqueous and the AH is bicarbonate-rich. Curiously, however, the CAIs reduce aqueous formation equally efficiently in eyes where the concentration of bicarbonate in plasma and aqueous is similar in human (Dailey et al, 1982;Toris et al, 2004), monkey (Wang et al, 1991), bovine (Shahidullah et al, 2003) and pig (Shahidullah et al, 2009).…”

Nonpigmented Ciliary Epithelial Cells Respond to Acetazolamide by a Soluble Adenylyl Cyclase Mechanism

“…[6][7][8][9] Carbonic anhydrase inhibitors target carbonic anhydrases with high selectivity, preventing catalysis of the reversible hydration of carbon dioxide to generate bicarbonate ions and protons. They reduce aqueous humor formation and intraocular pressure in all species that have been tested, including bovines, 10 rabbits, 11,12 dogs, 13 monkeys, 14 and humans, 15 as well as in the intact porcine eye. 16 Our past studies on ciliary epithelium of the porcine eye demonstrated robust expression of both membrane-bound (CAIV) and cytoplasmic (CAII) carbonic anhydrase in the NPE.…”

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

“…Acetazolamide reduces the rate of blood-to-aqueous 14 C-labelled bicarbonate movement (Zimmerman et al, 1976). This is in accordance with their ability to reduce AH formation in dogs (Maren, 1976) and rabbits (Caprioli and Sears, 1984;Kodama et al, 1985), species in which the CE concentrates bicarbonate from blood to aqueous and the AH is bicarbonate-rich. Curiously, however, the CAIs reduce aqueous formation equally efficiently in eyes where the concentration of bicarbonate in plasma and aqueous is similar in human (Dailey et al, 1982;Toris et al, 2004), monkey (Wang et al, 1991), bovine (Shahidullah et al, 2003) and pig (Shahidullah et al, 2009).…”

Nonpigmented Ciliary Epithelial Cells Respond to Acetazolamide by a Soluble Adenylyl Cyclase Mechanism

“…[6][7][8][9] Carbonic anhydrase inhibitors target carbonic anhydrases with high selectivity, preventing catalysis of the reversible hydration of carbon dioxide to generate bicarbonate ions and protons. They reduce aqueous humor formation and intraocular pressure in all species that have been tested, including bovines, 10 rabbits, 11,12 dogs, 13 monkeys, 14 and humans, 15 as well as in the intact porcine eye. 16 Our past studies on ciliary epithelium of the porcine eye demonstrated robust expression of both membrane-bound (CAIV) and cytoplasmic (CAII) carbonic anhydrase in the NPE.…”