Aspects on prostanoid and cholinergic effects on aqueous humour dynamics in human eyes

Abstract: The discovery of the ocular hypotensive effect of topically applied prostaglandins (PGs) has raised a number of questions about the mechanisms of action involved. The aim of the present thesis was to answer some of these questions.PGs reduce the intraocular pressure (IOP) by increasing uveoscleral flow through the ciliary muscle, but the exact mechanism is not known. Morphological changes may be involved. PGs are also involved in the inflammatory response. In the first study the aim was to investigate the effect of latanoprost, a prostaglandin F2 a-analogue, on the blood-aqueous barrier and the IOP restoration after long-term treatment. 26 glaucoma patients were treated with latanoprost (50 pg/ml) once daily for 6-12 months. Aqueous protein concentration was followed with a laser flare meter in 16 patients throughout this period. No change was observed. IOP increased slowly after withdrawal of treatment. It was concluded that latanoprost has no clinically significant effect on the permeability of the blood-aqueous barrier and that the IOP will return to pretreatment levels within a few weeks, indicating that any changes in the ciliary muscle morphology are reversible.In 20 healthy volunteers it was attempted to prevent the ocular hypotensive effect of latanoprost by inhibiting uveoscleral flow by a pronounced ciliary muscle contraction. For this purpose a high dose of the cholinergic agonist, physostigmine (1 drop 8 mg/ml alternate hours) was used. However, the effects on IOP of the two drugs were mainly additive most likely due to a short-lasting effect of physostigmine on the ciliary muscle.The progressive IOP reduction by physostigmine in the second study raised the question as to whether the drug reduces aqueous flow apart from enhancing outflow. On the contrary, in the third study repeated administrations of physostigmine, in 20 normal subjects, increased aqueous flow, measured with fluorophotometry, by about 25%.From studies of patients it is known that latanoprost twice daily has less ocular hypotensive effect than once daily. This was the subject of the two remaining studies. The possibility that latanoprost causes a short-lasting increase in aqueous flow was examined in 18 healthy volunteers. Application of a second drop in the morning would blunt some of the early IOP lowering effect of latanoprost. Once or twice daily applications had similar effect on aqueous flow, a tendency to an increase without any difference between the dose regimens. The next study confirmed the difference in effect on IOP between once and twice daily applications in 40 normal subjects. The difference remained even when one of the two applications was omitted after two weeks’ treatment. The results indicate that applying latanoprost twice daily induces a modest receptor desensitisation.