Small Molecule GSK-J1 Affects Differentiation of Specific Neuronal Subtypes in Developing Rat Retina

In this study, we focused on the role of potent histone demethylase inhibitor GSK-J1 as a blocker of Jumonji domain-containing protein 3 (Jmjd3) in early postnatal retinal development. Jmjd3 participates in different processes such as cell proliferation, apoptosis, differentiation, senescence, and cell reprogramming via demethylation of histone 3 lysine 27 trimethylation status (H3K27 me3). As a first approach, we determined the localization of Jmjd3 in neonate and adult rat retina. We observed that Jmjd3 accumulation is higher in the adult retina, which is consistent with the localization in the differentiated neurons, including ganglion cells in the retina of neonate rats. At this developmental age, we also observed the presence of Jmjd3 in undifferentiated cells. Also, we confirmed that GSK-J1 caused the increase in the H3k27 me3 levels in the retinas of neonate rats. We next examined the functional consequences of GSK-J1 treatment on retinal development. Interestingly, injection of GSK-J1 simultaneously increased the number of proliferative and apoptotic cells. Furthermore, an increased number of immature cells were detected in the outer plexiform layer, with longer neuronal processes. Finally, the influence of GSK-J1 on postnatal retinal cytogenesis was examined. Interestingly, GSK-J1 specifically caused a significant decrease in the number of PKC α-positive cells, which is a reliable marker of rod-on bipolar cells, showing no significant effects on the differentiation ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research