The prolactin/vasoinhibin axis regulates early postnatal retinal vascularization

Abstract

Purpose : The prolactin (PRL)/vasoinhibin axis is an emerging regulator of ocular blood vessels. PRL stimulates blood vessels growth (angiogenesis) but acquires antiangiogenic properties upon its cleavage to vasoinhibin, a PRL fragment that inhibits angiogenesis. Here, we investigated whether PRL modifies retinal angiogenesis in newborn mice exposed or not to high oxygen and whether the retinal conversion of PRL to vasoinhibin may be altered in the neonate mouse.

Methods : Newborn mice exposed or not to 75% oxygen from postnatal day (P) 6 to P8 were treated with PRL or vehicle twice a day from P5 through P8. Vascularization was assessed in flat-mounted retinas by the immunofluorescence staining of blood vessels. The cleavage of PRL to vasoinhibin was evaluated at P8 by the incubation of PRL with retinal extracts and Western blot. Quantitative RT-PCR determined the expression of PRL and the PRL receptor in the retina throughout the first week of postnatal life.

Results : PRL treatment elevated serum PRL levels (>300 ng/mL) and reduced the hyperoxia-induced inhibition of retinal angiogenesis, as revealed by a significant increase in retinal vascular density and expression of endothelial cell markers. The PRL cleaving protease, cathepsin D, generated 50% less vasoinhibin in the neonate than in the adult retina and such generation was further reduced under hyperoxia. The PRL and the PRL receptor mRNA are expressed in the retina during the first postnatal week.

Conclusions : PRL stimulates the angiogenesis of the retina in newborn mice under hyperoxia conditions. This proangiogenic action may be favored by the reduced conversion of PRL to vasoinhibin. PRL may be acting as a local regulator of retinal postnatal vascularization. Supported by CONACYT grant 289568.

This is a 2020 ARVO Annual Meeting abstract.