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Involvement of perivascular retinal tissue in the tone control of porcine retinal arterioles in vitro

Kim Holmgaard 


Disturbances in the retinal blood perfusion are believed to be involved in the pathophysiology of a variety of vision threatening retinal diseases. A prerequisite for understanding these disturbances is to have a detailed knowledge of how retinal perfusion is regulated under normal physiological conditions. This regulation involves both mechanisms in the vascular wall and in the perivascular retinal tissue.
The purpose of this project was to study the influence of the perivascular retinal tissue on the regulation of tone of porcine retinal arterioles in vitro. For this purpose, an experimental model was introduced that allows the study of pharmacological intervention on retinal vascular tone before and after removal of the perivascular tissue.
Using this model, it was found that the vasorelaxing effect of adenosine on retinal arterioles involves a direct action on cellular elements in the vascular wall that leads to relaxation of the vascular smooth muscle cells. Furthermore, adenosine was found to be synthesized by hydrolysis of ATP in the perivascular retinal tissue and ATP was shown to be released following stimulation of the glutamate NMDA receptors in this tissue. Finally, the vasorelaxation induced by stimulating the glutamate NMDA receptor is modified by GABA and is abolished by blocking the prostaglandin synthesis.
The observed reaction pattern may be part of a pathway that is especially active during ischaemia or high metabolic activity, where a regulation of the blood flow through vasodilation is needed. The findings may therefore contribute to a deeper understanding of the mechanisms underlying metabolic autoregulation of the retinal blood flow.