Prolactin improves retinal function in streptozotocin-induced diabetes

Abstract

Purpose : The function of the neural retina is compromised in diabetic retinopathy (DR). Preclinical studies show that high circulating levels of the hormone prolactin (PRL) mitigate electroretinogram (ERG) deficits induced by light-retinal damage. Here, we explored whether increased PRL circulating levels protect retinal function in the DR rat model injected with streptozotocin (STZ).

Methods : DB was induced in Wistar rats by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) and, four weeks after STZ, hyperprolactinemia was generated by a daily intraperitoneal administration of 20 mg/kg of sulpiride (a dopamine D2 receptor antagonist that stimulates the hypophyseal release of PRL into the circulation). In other experiments, osmotic minipumps delivering PRL were implanted one month after DB induction. Two weeks after sulpiride or PRL treatment, the functionality of the retina was evaluated by electroretinogram (ERG) or the screening of visual acuity with the opto-kinetic tracking (OKT) virtual optomotor system (OptoMotry; Cerebral Mechanics), respectively.

Results : Sulpiride increased serum PRL levels in DB rats compared to non-treated DB rats (4.4±0.9 to 50.1±5.8 ng/ml). The amplitude of the mesotopic ERG b-wave decreased in DB vs. non-DB rats (p<0.010) but no significant difference on a-wave amplitude was detected. The decrease in the b-wave due to DB was prevented by the treatment with sulpiride. Consistent with these findings, the visual acuity of diabetic rats was significantly reduced in DB vs. non-DB rats (p= 0.0137), and such reduction was prevented by the chronic delivery of PRL (p= 0.4226).

Conclusions : These findings support the neuroprotective effect of PRL against the damage of the neural retina due to DB and suggest the therapeutic value of sulpiride against DR. Supported by CONACYT grant 289568.

This is a 2020 ARVO Annual Meeting abstract.