Abstract
Purpose: :
The hormone prolactin (PRL) is present in milk from which it reaches the circulation of the offspring. Ocular tissues incorporate systemic PRL and proteolytically process it to vasoinhibins, a family of peptides with antiangiogenic properties that promote the apoptosis-mediated regression of the ocular hyaloid vessels. Here, we investigate whether a deficiency of PRL in milk reduces the levels of intraocular vasoinhibins and the apoptosis of the hyaloid vasculature in neonatal rats.
Methods: :
On postpartum days 4 to 18, lactating rats were injected with bromocriptine, an inhibitor of pituitary PRL secretion, with bromocriptine and ovine PRL (delivered via an osmotic minipump), or with vehicle. Serum PRL levels in lactating mothers and pups were measured by the Nb2 cell-bioassay. Apoptosis and vasoinhibin levels were measured by ELISA and Western blot, respectively, in pups’ eye extracts.
Results: :
Bromocriptine reduced serum PRL by 75% in mothers and pups and was associated with a significant decrease of offspring body weight at postnatal days (PND) 16 and 18. Treating the bromocriptine-injected mothers with PRL increased by two-fold the circulating levels of the hormone in both mothers and pups, and it reversed the loss of offspring body weight. Moreover, bromocriptine lowered the levels of retinal vasoinhibins in the nursing young. Consistent with the expected times for the apoptosis of the ocular hyaloid vasculature, eye apoptosis increased three-fold between PND 8 and 12, and declined on PND 18. Bromocriptine significantly reduced ocular apoptosis on PND 8 and 12, and this reduction was prevented by exogenous PRL.
Conclusions: :
Lowering PRL in the mother reduces circulating PRL, retinal vasoinhibins, and ocular apoptosis in the nursing young. These findings are consistent with PRL in milk entering the circulation of the nursing young and contributing to the physiological involution of the hyaloid vasculature via its intraocular conversion to vasoinhibins. These findings could help explain the observation that breastfeeding protects against retinopathy of prematurity, perhaps via milk PRL promoting vasoinhibin-mediated regression of the neovessels.
Keywords: retinopathy of prematurity • development • apoptosis/cell death