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M. Ramirez, Z. Wu, B. Moreno-Carranza, M. C. Jeziorski, G. Martinez de la Escalera, P. Colosi, C. Clapp; An AAV2 Vasoinhibin Vector Protects Against Increased Retinal Vasopermeability in Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2526.
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© ARVO (1962-2015); The Authors (2016-present)
Proteolysis of the hormone prolactin generates vasoinhibins, a family of peptides that are able to inhibit the pathological increase in retinal vasopermeability (RVP) associated with diabetes (JCI 118:2291, 2008). Here, we tested the ability of an adeno-associated virus type-2 (AAV2) vasoinhibin vector to inhibit diabetes-induced RVP.
AAV2 vectors expressing vasoinhibin, prolactin, or soluble VEGF receptor 1 (sFlt-1) (2.8 X 1010 vg/eye) were injected intravitreally into the eyes of rats. Four weeks later the animals were treated with streptozotocin to induce diabetes. After one month, RVP was evaluated using the Evans Blue dye method. RT-PCR of retinal extracts and Western blot analysis of the conditioned medium of vector-transduced HEK293 cells confirmed the expression and secretion of the various proteins encoded by the vectors.
In rats receiving intravitreal injection of vehicle, diabetes induced a significant increase in RVP compared to non-diabetic controls (49.0 ± 3.1 vs. 30.4 ± 2.9 µl plasma/g retina x h, p<0.001). This increase was prevented by intravitreal injection of the AAV2 vasoinhibin vector (29.1 ± 2.5 vs. 49.0 ± 3.1 µl plasma/g retina x h, p<0.001). In contrast, treatment with the AAV2 prolactin vector (44.3 ± 2.0 µl plasma/g retina x h, p<0.235) or the AAV2 sFlt-1 vector (37.5 ± 4.1 µl plasma/g retina x h, p<0.065) did not significantly block RVP in diabetic rats.
These results suggest that AAV2 vasoinhibin vectors may have therapeutic value for controlling the pathological increase in RVP associated with diabetic retinopathy in the clinic.
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