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The basal tone regulation of retinal arterioles with special reference to acidosis and vasomotion

Anders Hessellund

Summary

Disturbances in the regulation of retinal blood flow are involved in the pathophysiology of a variety of sight threatening diseases such as diabetic retinopathy. Therapeutic intervention on these diseases on a rational basis requires a detailed knowledge of the mechanisms involved in the regulation of the retinal blood flow under normal conditions. These mechanisms include metabolic autoregulation influenced by pH and probably other metabolites, and vasomotion dependent on intracellular signaling molecules such as [Ca2+]i and cGMP.
These mechanisms were investigated using an in vitro setup with a myograph for isometric recording of the tension of the vascular wall. In addition,
experimental setups were established to: 1) monitor the [Ca2+]i in the retinal arteriolar wall and in single smooth muscle cells in the wall, and 2) monitor the membrane potential of the smooth muscle cells. The experiments were carried out on porcine retinal arterioles (inner diameter approximately 150 μm), and confirming experiments were carried out on retinal arterioles from two human eyes.
The experiments showed that acidosis elicited a relaxation of isolated retinal arterioles which was independently of NO synthesis. The acidosis induced
vasorelaxation was accompanied with a decrease in [Ca2+]i and a hyperpolarisation of the membrane potential. There were no differences between the effect induced by normocapnic and hypercapnic acidosis on the parameters monitored.
Vasomotion could be initiated and maintained with a frequency of 0.82±0.06 min-1 and an amplitude of 0.041±0.005 N/m. Cyclic GMP reduced the frequency of vasomotion and oscillations in the [Ca2+]i, without affecting the amplitude. This was accompanied with a reduction of the spontaneous oscillations in.
The experiments have increased the knowledge of mechanisms involved in the regulation of tone in retinal vascular smooth muscle cells. This evidence points
at relevant in vivo and in vitro examinations for further exploring the regulation of the retinal blood flow in order to point at potential new therapeutic modalities for the treatment of disturbances in retinal flow regulation.