Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. P SF was expressed in all retinal cell types examined in vitro, but immunohis tochemical analysis revealed PSF mainly associated with retinal vessels. PS F expression was constitutive in retinal pericytes (RPCs) but could be modu lated in bovine retinal capillary endothelial cells (RECs) by cell confluen cy, hypoxia, serum starvation, high glucose concentrations, or inversely by soluble factors present in early vs. late retinopathy, such as TGF-beta, V EGF, or bFGF. In addition, RPC-conditioned media dramatically increased REC PGI2 production, a response inhibited by blocking PSF with a specific anti sense oligodeoxynucleotide (ODN). In vivo, PGI2 increased retinal blood flo w (RBF) in control and diabetic animals. Furthermore, the early drop in RBF during the initial weeks after inducing diabetes in rats, as well as the l ater increase in RBF, both correlated with levels of retinal PSF. RBF also responded to treatment with RPC-conditioned media, and this effect could be partially blocked using the antisense PSF ODN. We conclude that PSF expres sed by ocular cells can induce PGI2, retinal vascular dilation, and increas ed retinal blood flow, and that alterations in retinal PSF expression may e xplain the biphasic changes in RBF observed in diabetes.