Danish Medical Bulletin - No. 2. June 2004. Vol. 51 Page 216.

ABSTRACT OF PhD DISSERTATION

Carbonic anhydrase inhibition: The effect on retinal
and optic nerve oxygenation
and the mechanisms of action

Daniella Bach Pedersen

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This PhD dissertation was accepted by The Faculty of Health Sciences of the University of Copenhagen, and was defended on February 9, 2004 .

Official opponents: Oliver Arend, Germany, Niels Chresten Berg Nyborg, and Michael Larsen.

Tutors: Peter Koch Jensen, Morten la Cour, Einar Stefànsson, Iceland, and Martin Lauritzen.

Correspondence: Daniella Bach Pedersen, Department of Ophthalmology, 2061. H:S Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø.
E-mail: Daniella@dadlnet.dk

Dan Med Bull 2004;51:216.

ABSTRACT

Carbonic anhydrase inhibitor (CAI) is a drug widely used in the treatment of glaucoma; it lowers the intraocular pressure (IOP) by inhibiting the production of aqueous humour. It has been shown that systemically administered CAIs increase the optic nerve oxygen tension (ONPO 2 ) in pigs - also when IOP is kept constant.

The purpose of this study was to find out whether CAIs have the same effect on the retinal oxygen tension (RPO 2 ) as it has on ONPO 2 and to investigate the mechanisms of action of the effect of CAI.

The experiments were carried out on young, healthy pigs, since the porcine eye has similar circulatory properties as does the human eye.

Our results are as follows:

  1. CAI increases RPO 2 as much as it increases ONPO 2 when 500 mg dorzolamide is given intravenously.

  2. A significant vasodilatation of the retinal arterioles and venules is seen when 500 mg dorzolamide is given intravenously. Vasodilatation is probably the reason why ONPO 2 and RPO 2 increase.

  3. Lowering IOP with another glaucoma drug, timolol (a beta-blocker), did not increase ONPO 2 , indicating that lowering IOP per se does not increase ONPO 2 . Thus, CAIs' increasing effect on ONPO 2 is not due to the IOP lowering effect.

  4. ONpH decreases during carbonic anhydrase inhibition, metabolic and respiratory acidoses.

  5. The ONpH lowering effect of CAI per se is not the cause of the ONPO 2 increase.

  6. CO 2 accumulation imitates the ONPO 2 increasing effect of CAI, indicating that CO 2 accumulation is a possible mechanism of action in CAIs' effect on ONPO 2 .

  7. Inhibiting prostaglandin synthesis by giving indomethacin intravenously decreases ONPO 2 . Additionally it diminishes the effect on ONPO 2 of carbonic anhydrase inhibition and CO 2 accumulation. It is therefore likely that the effect of CAI is at least partly due to the effect of prostaglandins.

It remains to be shown if CAIs may counter hypoxia and prevent ischaemia by opposing vasoocclusion in ischaemic conditions in the retina and optic nerve. It should be investigated if our results are applicable in clinical settings, eventually offering a pharmacological treatment of retinal ischemia.
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