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Experimental Models for Study of Retinal Pigment Epithelial Physiology and Pathophysiology
Published on: November 7, 2010
Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor
Y Hata1, A Clermont, T Yamauchi
1Research Division, Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, USA.
The Journal of Clinical Investigation
|August 23, 2000
Summary
Prostacyclin-stimulating factor (PSF) regulates retinal blood flow by influencing prostacyclin (PGI2) production. Altered retinal PSF levels may explain changes in blood flow observed in diabetes.
Area of Science:
- Ophthalmology
- Vascular Biology
- Endocrinology
Background:
- Prostacyclin-stimulating factor (PSF) stimulates prostacyclin (PGI2) synthesis, a key vasodilator.
- Retinal blood flow (RBF) regulation is crucial for ocular health, and its dysregulation is implicated in diabetic retinopathy.
Purpose of the Study:
- To investigate the expression, regulation, and hemodynamic effects of PSF in the retina.
- To determine the role of PSF in mediating changes in RBF, particularly in diabetes.
Main Methods:
- Immunohistochemistry to localize PSF in retinal tissues.
- In vitro studies using cultured retinal pericytes (RPCs) and endothelial cells (RECs) to examine PSF expression and regulation.
- In vivo studies in rats to assess the impact of PSF on RBF, including in diabetic models.
- Use of antisense oligodeoxynucleotides (ODNs) to block PSF activity.
Main Results:
- PSF is expressed in retinal cells, primarily associated with vessels, and its expression in RECs is modulated by various factors including hypoxia and growth factors.
- RPC-conditioned media enhanced PGI2 production in RECs, an effect inhibited by PSF-specific antisense ODN.
- In vivo, PGI2 increased RBF in control and diabetic rats.
- Retinal PSF levels correlated with RBF changes in diabetic rats, and antisense PSF ODN partially blocked the effects of RPC-conditioned media on RBF.
Conclusions:
- PSF produced by ocular cells induces PGI2, leading to retinal vasodilation and increased RBF.
- Altered retinal PSF expression is a potential mechanism underlying the biphasic changes in RBF observed in diabetes.
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