Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels

Abstract

Retinal and optic nerve oxygen tension increased with systemic administration of dorzolamide. The retinal vessels dilated, probably causing increased blood flow inducing the observed increase in RPO2. The increased oxygenation of retina by CAI may offer therapeutic possibilities in ischaemic diseases of the retina and optic nerve.

Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs

“…), or the isoforms involved in it, are unknown for the moment. [25][26][27][28][29][30] In line with these studies, 25-30 a very recent report shows that indapamide 6.10 has a protective role against ischemia-induced injury and dysfunction of the blood-brain barrier, probably due to its vasodilating effects. 31,32 An organ-protective effect of indapamide in animal models of renal failure has also been reported, showing the drug to be beneficial in preventing damage to the capillary structures, the endothelium, and in reducing the hypertrophy of superficial glomeruli among others.…”

“…2 On the other hand, classical sulfonamide CAIs such as acetazolamide 6.1, methazolamide 6.2 ethoxzolamide 6.3, and other compounds possessing such properties are known to induce vasodilation in a variety of tissues and organs, including the kidneys, eye vasculature, brain vessels, and so on. [25][26][27][28][29][30] However, the exact mechanisms by which they produce this beneficial effect for many pathologies (e.g., hypertension, glaucoma, diabetic retinopathy, etc. ), or the isoforms involved in it, are unknown for the moment.…”

“…16,17,33 All these effects are probably mediated by inhibition of CAs present in blood vessels or in the kidneys, but no specific pharmacological or biochemical studies are available so far, except for these clinical observations mentioned here. [28][29][30][31][32][33] The lesson we learned from all these data is that probably many of the recently reported beneficial clinical properties of indapamide 6.10 are indeed due to its diuretic effects, but in conjunction with its strong inhibition of some CA isozymes (such as CA IV, VB, VII, IX, XII, and/or XIII) reported here for the first time, isoforms present in kidneys and blood vessels. This hypothesis may explain both the blood pressure lowering effects and organprotective activity of the drug.…”

Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging

“…Measurements of oxygen tension overlying the optic nerve and retina have been reported in numerous animal studies; [5][6][7][8][9] however, the technique involves the intraocular insertion of microelectrodes which is technically demanding and invasive. Phosphorescence imaging has been performed in experimental glaucoma in animals, 10,11 but requires the injection of a bolus of an oxygen chemical probe whose safety in humans has yet to be determined.…”

The Multifactorial Nature of Retinal Vascular Disease

“…Clinicians and scientists have been intrigued by this remarkable efficacy, and thus the in vivofunction of CA has been thoroughly investigated with some fascinating results. Firstly, there are multiple reports that CA inhibition reduces macular leakage and edema, with additional data suggesting that CA inhibitors may increase oxygen tension and the retinal arteriole diameter [30,45]. In a study by Gao et al [46], substantial levels of CA were detected in vitreous samples from patients with inactive PDR as well as moderate-to-severe nonproliferative DR.…”