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S.H. Poor, C. Mailhos, J. Bradley, L. Mullin, G.S. Robinson, D.T. Shima; PV–1 Gene Expression Predicts the Loss of Blood Retinal Barrier Function: A Novel Marker of Retinal Vascular Leakage . Invest. Ophthalmol. Vis. Sci. 2006;47(13):502.
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The blood retinal barrier (BRB) is compromised in many diseases of the retina with increased extravasation from the retinal vasculature. Since the endothelial protein PV–1 is localized to organelles responsible for permeability such as fenestrae and caveolae, it may serve as a marker for vascular permeability in the retina. The goal of this study is to characterize PV–1 gene expression in retinal vasculature during normal development and in pathological angiogenesis using a murine model of retinopathy.
PV1 protein and mRNA expression was determined in the developing mouse retina from day 3 (P3) to day 60 (P60). PV1 protein was measured in frozen retinal sections and retinal whole mounts using immunofluorescence. PV1 protein expression was quantified using a standardized image capture procedure followed by pixel intensity measurements. PV–1 mRNA was quantified using qRT– PCR in isolated retinas collected at the same time points used for protein measurement. In the ROP model, P7 mouse pups and nursing mothers were placed in 75% oxygen for five days and then returned to room air. PV1 protein and mRNA expression were examined at ages P8, P10, P12, P13, P15, P17, P20 and P23
We examined PV1 expression in the retinal vasculature during development and found PV1 protein and mRNA levels maximally expressed at P6. There is a progressive decrease in PV1 expression from P6 to P10 with minimal expression of PV–1 protein in retinal vasculature thereafter. Using 4KDa FITC–dextran as a measure of vascular leakage, we have previously demonstrated that the blood retinal barrier forms at P10 and note that a decrease in PV–1 expression correlates with the formation of the BRB. PV1 expression in the choroidal vasculature does not change during development. In the ROP model, there is no significant difference in PV1 mRNA or protein expression at P8, P10 or P12 compared to controls. PV1 mRNA is increased in ROP mice at P13, reaches a maximum at P15, and decreases to control levels by P20. PV1 protein is concentrated at the avascular border and is found to be maximal in neovascular tufts and in the superficial retinal vasculature.
Changes in PV1 gene expression in retinal vessels during development and in pathological angiogenesis correlate with retinal vascular leakage and may be useful in the study and treatment of retinal vascular disease.
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