Sulpiride-induced hyperprolactinaemia increases retinal vasoinhibin and protects against diabetic retinopathy in rats.

Autor: Adán-Castro E; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Siqueiros-Márquez L; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Ramírez-Hernández G; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Díaz-Lezama N; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Ruíz-Herrera X; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Núñez FF; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Núñez-Amaro CD; Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Querétaro, México., Robles-Osorio ML; Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Querétaro, México., Bertsch T; Institute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital & Paracelsus Medical University, Nuremberg, Germany., Triebel J; Institute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital & Paracelsus Medical University, Nuremberg, Germany., Martínez de la Escalera G; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México., Clapp C; Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, México.
Jazyk: angličtina
Zdroj: Journal of neuroendocrinology [J Neuroendocrinol] 2022 Apr; Vol. 34 (4), pp. e13091. Date of Electronic Publication: 2022 Jan 25.
DOI: 10.1111/jne.13091
Abstrakt: Excessive vasopermeability and angiogenesis compromise vision in diabetic macular oedema (DME) and diabetic retinopathy (DR). Vasoinhibin is a fragment of the hormone prolactin (PRL) that inhibits diabetes-induced retinal hypervasopermeability and ischaemia-induced retinal angiogenesis in rodents. Hyperprolactinaemia generated by the dopamine D2 receptor antagonist, levosulpiride, is associated with higher levels of vasoinhibin in the vitreous of patients with DR, implying a beneficial outcome due to vasoinhibin-mediated inhibition of retinal vascular alterations. Here, we tested whether hyperprolactinaemia induced by racemic sulpiride increases intraocular vasoinhibin levels and inhibits retinal hypervasopermeability in diabetic rats. Diabetes was generated with streptozotocin and, 4 weeks later, rats were treated for 2 weeks with sulpiride or osmotic minipumps delivering PRL. ELISA, Western blot, and Evans blue assay were used to evaluate serum PRL, retinal vasoinhibin, and retinal vasopermeability, respectively. Hyperprolactinaemia in response to sulpiride or exogenous PRL was associated with increased levels of vasoinhibin in the retina and reduced retinal hypervasopermeability. Furthermore, sulpiride decreased retinal haemorrhages in response to the intravitreal administration of vascular endothelial growth factor (VEGF). Neither sulpiride nor exogenous PRL modified blood glucose levels or bodyweight. We conclude that sulpiride-induced hyperprolactinaemia inhibits the diabetes- and VEGF-mediated increase in retinal vasopermeability by promoting the intraocular conversion of endogenous PRL to vasoinhibin. These findings support the therapeutic potential of sulpiride and its levorotatory enantiomer, levosulpiride, against DME and DR.
(© 2022 British Society for Neuroendocrinology.)
Databáze: MEDLINE
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