NO and myogenic mechanisms in choroidal autoregulation

For a long time it has been assumed that the choroid is a strictly passive vascular bed showing no autoregulation. In the recent years there is, however, evidence that the choroid shows some degree of autoregulation in response to both increase and decrease in ocular perfusion pressure. This evidence arises from animal and human studies. In a previous project we have investigated some of the mechanisms underlying choroidal blood flow regulation during isometric exercise. In these studies in healthy subjects we were able to identify that the L-arginine/nitric oxide (NO) system as well as the endothelin system are involved in the processes that regulate choroidal blood flow in face of the increase in perfusion pressure. The aim of the experiments scheduled in this grant proposal is to further elucidate mechanisms of choroidal autoregulation in humans. Whereas we have identified that NO plays a role in choroidal blood flow regulation during isometric exercise the source of this NO remains to be elucidated. Unfortunately specific NO synthase inhibitors for human use are currently not available. Hence, we will investigate in a well established rabbit model whether the NO regulating choroidal blood flow is from endothelial or neural sources. Another experiment is designed to investigate whether NO also plays a role in choroidal blood flow regulation during a decrease in ocular perfusion pressure. This question will be answered in a study in healthy humans during an experimental increase in intraocular pressure. Finally, experiments are scheduled to investigate whether a myogenic mechanism may be involved in choroidal autoregulation in healthy humans. Previous studies in the rabbit indicate that this may be the case, because the autoregulatory range of the choroid was dependent not only on the change in perfusion pressure, but also on the intraocular pressure value. We aim at investigating this behaviour in the human choroid by combining isometric exercise with an experimental increase in intraocular pressure using a suction cup. The scheduled experiments will help to further understand our knowledge of choroidal blood flow regulation.