Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom.
PLoS One. 2012;7(4):e34531. doi: 10.1371/journal.pone.0034531. Epub 2012 Apr 5.
Photosensitive retinal ganglion cells (pRGCs) respond to light from birth and represent the earliest known light detection system to develop in the mouse retina. A number of morphologically and functionally distinct subtypes of pRGCs have been described in the adult retina, and have been linked to different physiological roles. We have previously identified two distinct isoforms of mouse melanopsin, Opn4L and Opn4S, which are generated by alternate splicing of the Opn4 locus. These isoforms are differentially expressed in pRGC subtypes of the adult mouse retina, with both Opn4L and Opn4S detected in M1 type pRGCs, and only Opn4L detected in M2 type pRGCs. Here we investigate the developmental expression of Opn4L and Opn4S and show a differential profile of expression during postnatal development. Opn4S mRNA is detected at relatively constant levels throughout postnatal development, with levels of Opn4S protein showing a marked increase between P0 and P3, and then increasing progressively over time until adult levels are reached by P10. By contrast, levels of Opn4L mRNA and protein are low at birth and show a marked increase at P14 and P30 compared to earlier time points. We suggest that these differing profiles of expression are associated with the functional maturation of M1 and M2 subtypes of pRGCs. Based upon our data, Opn4S expressing M1 type pRGCs mature first and are the dominant pRGC subtype in the neonate retina, whereas increased expression of Opn4L and the maturation of M2 type pRGCs occurs later, between P10 and P14, at a similar time to the maturation of rod and cone photoreceptors. We suggest that the distinct functions associated with these cell types will develop at different times during postnatal development.
感光性视网膜神经节细胞（pRGCs）自出生起便对光产生反应，是在小鼠视网膜中发育的最早已知的光检测系统。在成年视网膜中已经描述了多种形态和功能上不同的 pRGCs 亚型，并与不同的生理作用相关联。我们之前已经鉴定出两种不同的小鼠黑视蛋白异构体，Opn4L 和 Opn4S，它们是由 Opn4 基因座的选择性剪接产生的。这些异构体在成年小鼠视网膜的 pRGC 亚型中差异表达，Opn4L 和 Opn4S 均在 M1 型 pRGCs 中检测到，而仅在 M2 型 pRGCs 中检测到 Opn4L。在这里，我们研究了 Opn4L 和 Opn4S 的发育表达，并显示了在出生后发育过程中的差异表达谱。Opn4S mRNA 在整个出生后发育过程中保持相对恒定的水平，Opn4S 蛋白水平在 P0 至 P3 之间显示出明显增加，然后随着时间的推移逐渐增加，直到 P10 达到成年水平。相比之下，Opn4L mRNA 和蛋白水平在出生时较低，与早期时间点相比，在 P14 和 P30 时显著增加。我们认为这些不同的表达谱与 M1 和 M2 型 pRGCs 的功能成熟有关。基于我们的数据，表达 Opn4S 的 M1 型 pRGCs 首先成熟，是新生鼠视网膜中的主要 pRGC 亚型，而 Opn4L 的表达增加和 M2 型 pRGCs 的成熟发生在 P10 和 P14 之间，与 rod 和 cone 光感受器的成熟时间相似。我们认为，与这些细胞类型相关的不同功能将在出生后发育的不同时间发展。
