High Levels of Circulating Prolactin Mitigate the Retinal Vasopermeability Increase in Diabetic Rats

Abstract

Purpose: : Vasoinhibins are proteolytically derived fragments of the hormone prolactin (PRL) that prevent the excessive retinal vasopermeability (RVP) associated with diabetes (JCI 118:2291, 2008). Here, we investigate whether circulating PRL, by serving as a source of intraocular vasoinhibins, is able to reduce diabetes-induced RVP.

Methods: : Hyperprolactinemia was induced in Wistar rats by placing two anterior pituitary grafts under the kidney capsule for 15 days. The levels of PRL in serum and of PRL and vasoinhibins in the vitreous were measured by ELISA and by immunoprecipitation-Western blot, respectively. Non-grafted (control) and anterior pituitary-grafted rats were then injected (i.p.) for 75 days with streptozotocin to induce diabetes, after which RVP was determined by the Evans blue method.

Results: : Systemic and intravitreal levels of PRL and vasoinhibins were two-fold higher in anterior pituitary-grafted rats than in controls. Treatment of grafted rats with the dopaminergic agonist bromocriptine (injected i.p. for 15 days before sacrifice) reduced circulating and vitreous PRL and vasoinhibin to basal levels. Diabetes induced a 1.3-fold increase in RVP in grafted rats, a level that was significantly lower than the 2-fold increase observed in control rats. Reducing circulating PRL levels with bromocriptine increased RVP in the grafted rats.

Conclusions: : Higher levels of circulating PRL are associated with increased concentrations of intravitreal vasoinhibins and lower RVP in diabetic rats. These findings suggest that hyperprolactinemia protects against excessive retinal vasopermeability in diabetic retinopathy, presumably through the increased generation of intraocular vasoinhibins.

Keywords: diabetic retinopathy • growth factors/growth factor receptors • diabetes