Abstract
Purpose: :
Disturbances in the regulation of the retinal blood flow are involved in the pathophysiology of a variety of sight threatening diseases, including diabetic retinopathy. Therapeutic intervention on these diseases requires a detailed knowledge of the cells and pharmacological mechanisms involved in the regulation of the tone in retinal resistance arterioles. It has been shown that the vasodilating effect of ATP but not adenosine depends on the perivascular retinal tissue, but the factors responsible for this effect in the perivascular retina are unknown.
Methods: :
Porcine retinal arterioles (mean diameter 150 µm), with a rim of surrounding retina, were mounted in a wire myograph (DMT) and placed in a Zeiss LSM 5 Exciter confocal microscope allowing for simultaneous recording of vascular tone and calcium activity. The preparations were loaded with the calcium sensitive fluorophore Oregon Green and were pre-contracted with the prostaglandin analogue U46619 (10-6 M). The vascular tone and changes in calcium activity in the perivascular cells were studied after addtion of increasing concentrations of adenosine and ATP.
Results: :
Both adenosine and ATP reduced the tone of the retinal arterioles in the presence of the perivascular retina (p<0.05). In isolated vessels, adenosine, but not ATP, significantly reduced the intracellular calcium activity in the vascular smooth muscle cells (p<0.01). On the contrary, ATP, but not adenosine, increased the calcium activity in perivascular cells located on the lateral aspects of the arterioles immediately external to the vascular smooth cells(p>0.01).
Conclusions: :
Perivascular retinal cells participate in the regulation of retinal vascular tone through mechanisms that involve ATP. Adenosine produced by degradation from ATP induces vasodilation by a direct effect on retinal vascular smooth muscle cells.
Keywords: retina • retinal glia • calcium