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David Arredondo, Olivia Baldivieso Hurtado, Daniel Ochoa-Contreras, Carmen Clapp, Stephanie Thebault; Vasoinhibins reduce the increase of retinal vasopermeability associated with diabetes: contribution of the kallikrein-kinin system. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2696. doi: https://doi.org/.
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Vasoinhibins are proteolytically-derived fragments of the hormone prolactin that prevent excessive retinal vasopermeability (RVP) associated with diabetes (JCI 118:2291, 2008). The kallikrein-kinin system has been shown to contribute to RVP increase associated with diabetes by enhancing bradykinin (BK) production (Nat Med 13:181, 2007) and inducing B1 receptor expression (PloS One 7:e33864, 2012). Here we investigated if vasoinhibins could attenuate the increase of RVP induced by the intravitreal injection of BK as well as the induction of B1 receptor expression in diabetes.
The RVP was quantified by the Evans blue method in Wistar male rats that were injected intravitreously with BK (1 nM), combined or not with vasoinhibins (1 µM) or a B2 receptor antagonist (HOE-140). The retinal expression of B1 receptor mRNA was quantified by real-time pcr in two models: 1) healthy rats intravitreously injected with vitreous from patients with proliferative diabetic retinopathy (PDR) for 48 h, and 2) rats rendered diabetic by i.p. streptozotocin for 4 weeks. Both models were also subjected to intra-vitreous injection of vasoinhibins for the last 24 h.
Intravitreal injection of BK resulted in a two-fold increase in RVP compared to saline. Vasoinhibins prevented the BK effect on RVP, as did the B2 receptor antagonist Hoe-140. In addition, mRNA levels of B1 receptor were increased by four- and two-fold in retinas from rats injected with vitreous from PDR patients and diabetic rats compared to rats injected with vitreous from non-diabetic patients and controls, respectively. Notably, vasoinhibins prevented the induction of B1 receptor expression in both models.
Vasoinhibins reduce the BK-induced increase of RVP and the induction of B1 receptor expression related to diabetes.
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