Novel Cellular Bouton Structure Activated by ATP in the Vascular Wall of Porcine Retinal Arterioles

Abstract

The vasodilating effect of purines in porcine retinal tissue involves ATP-dependent calcium activity in a layer of cellular boutons located external to the vascular smooth muscle cells and internal to the perivascular glial cells.

Prostaglandin induced changes in the tone of porcine retinal arterioles in vitro involve other factors than calcium activity in perivascular cells

“…The present study confirms results from previous studies that PGE 2 can induce concentration dependent relaxation and PGF 2 a a less pronounced contraction of porcine retinal arterioles in vitro (Holmgaard and Bek, 2010;Misfeldt et al, 2010a;Yu et al, 2001). The protocol used to study the effects of the two prostaglandins was designed to elicit opposite tone responses which required that the relaxing effect of PGE 2 was studied after pre-contraction (Holmgaard and Bek, 2010).…”

“…The PVCs located outside the retinal arteriolar smooth muscle cells have previously been shown to have increased Ca 2þ activity simultaneously with relaxation induced by both ATP and PGE 2 (Misfeldt et al, 2013(Misfeldt et al, , 2010a, but in the present study a similar increase in Ca 2þ activity was observed in these cells during contraction induced by both the prostaglandin analogue U46619, PGF 2a and the unspecific depolarizing agent KPSS. An involvement of the PVCs in the modulation of vascular tone might be expected to depend on recruitment through different Ca 2þ channels during contraction and relaxation.…”

“…The position of the myograph in the confocal microscope was adjusted to allow the PVC layer to be in focus using a 40Â objective and 0.7Â zoom, as described previously (Misfeldt et al, 2010a). Excitation was performed using an argon laser at 488 nm, fluorescence was collected at >530 nm, and the pinhole width and the detector gain of the confocal microscope were adjusted to ensure that recordings of fluorescence intensity were below the saturation level (Misfeldt et al, 2010b), and the thickness of the optical section was 10.6 mm.…”

“…This autoregulation includes myogenic control that maintains the retinal blood flow constant during changes in the systemic blood pressure and diameter changes that compensate for changes in retinal metabolism (Bosch et al, 2009;Garhofer et al, 2003;Jeppesen et al, 2007). The cellular basis for retinal autoregulation is unknown, but recently a new type of perivascular cell (PVC) with pericyte characteristics was identified in the retinal arterial vascular wall immediately external to the smooth muscle cells but internal to the perivascular glial cells (Misfeldt et al, 2010a). These cells displayed calcium activity during relaxation of retinal arterioles in vitro and had processes extending into the perivascular retina (Misfeldt et al, 2013), but the source of Ca 2þ recruitment in this cell type is unknown.…”

Purinergic Mechanisms and Prostaglandin E Receptors Involved in ATP-Induced Relaxation of Porcine Retinal Arterioles in vitro

“…Thus, it has been shown that ATP stimulates intracellular calcium activity in perivascular cells [34,35], and intracellular calcium levels are elevated in retinal cell cultures exposed to hyperglycaemia [8]. Furthermore, retinal blood flow is affected by activation of P 2 receptors in alloxan-induced diabetes in rabbits [36,37], and a recent study has shown that ATP relaxation of porcine retinal arterioles exposed to hypercholesterolaemia in vivo is modified by both hepatic low-density lipoprotein receptor deficiency and diabetes mellitus [38].…”