Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
Adv Exp Med Biol. 2010;664:21-8. doi: 10.1007/978-1-4419-1399-9_3.
The molecular signals governing retinal development remain poorly understood, but some key molecules that play important roles have been identified. Activation of STAT3 by cytokines such as LIF and CNTF specifically blocks differentiation of rod photoreceptors. Here we test the hypothesis that PKC activation promotes development of rod photoreceptors by inhibiting STAT3. Explant cultures of mouse retina were used to study the effects of PKC activation on rod development. The expression of opsin, a rod specific marker, is induced at an early stage in retina explants cultured in the presence of PMA and this effect is prevented by the PKC inhibitor Go7874. Histological experiments show that there is expression of PKC beta1, but not PKC-alpha in the outer nuclear layer between E17.5 and PN5. In vitro data derived from cell lines shows that activation of PKC results in reduction of STAT3 phosphorylation. In addition, inhibition of PKC results in increase STAT3 phosphorylation. We suggest that cross talk of signals between STAT3 and PKC may determine the differentiation of rods from retinal progeitors.
分子信号调控视网膜发育的机制仍不清楚，但已经鉴定出一些发挥重要作用的关键分子。细胞因子如 LIF 和 CNTF 激活 STAT3 可特异性阻止视杆细胞分化。在这里，我们通过实验验证了假设，即 PKC 激活通过抑制 STAT3 促进视杆细胞的发育。我们使用小鼠视网膜的外植体培养物来研究 PKC 激活对视杆发育的影响。在 PMA 存在下培养的视网膜外植体中，视蛋白（一种视杆特异性标记物）的表达在早期被诱导，而 PKC 抑制剂 Go7874 可阻止这种效应。组织学实验表明，在 E17.5 至 PN5 期间，PKC beta1 而不是 PKC-alpha 在外核层中有表达。细胞系的体外数据表明，PKC 的激活导致 STAT3 磷酸化减少。此外，PKC 的抑制导致 STAT3 磷酸化增加。我们认为，STAT3 和 PKC 之间的信号串扰可能决定了视网膜祖细胞向视杆细胞的分化。
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