Inhibition of carbonic anhydrase is an important principle for the treatment of glaucoma. The effect is assumed to be due to an inhibition of aqueous humor production in the ciliary body with a resulting reduction in the intraocular pressure that protects the eye from ischemic damage.
1 2 3 However, evidence suggests that the effect may also be due to a relaxation of the blood vessels in and around the optic nerve head, so that the perfusion of these structures is improved and tissue ischemia is prevented.
1 4 5 Thus, carbonic anhydrase inhibitors (CAIs) have been shown to have a vasodilating effect on the blood vessels in the retina and the optic nerve from animals both in vitro
1 and in vivo,
5 and in the human retina in vivo,
2 an effect that has been shown to be independent of NO.
6 The enzymatic effect of carbonic anhydrase is to hydrate carbon dioxide to carbonic acid, which dissolves spontaneously into protons and bicarbonate according to the equation: CO
2+H
2O↔H
2CO
3↔ H
++HCO
3 −. However, since the concentration of metabolites on each side of the equation is unknown in vivo, it is also unknown in which direction and driven by which metabolites the reaction may be catalyzed by CAI to induce vasodilation. Previous experiments on retinal arterioles from experimental animals have shown that hypercapnic and normocapnic acidosis have different effects on the retinal metabolism.
7 The two acidosis forms induce the same degree of vasodilation in pial
8 and retinal
9 arterioles, which may indicate that the mechanism of action of vasodilation is through H
+, but other in vivo experiments in pigs have shown a lack of vasodilating effect of metabolic acidosis induced by intravenous infusion of NH
4Cl.
10 However, it is likely that mechanisms other than the enzymatic effect on carbonic anhydrase may contribute to the vasodilating effect of CAI,
11 and recent experiments have suggested that the perivascular retinal tissue may be involved in the effect.
12