Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation.

Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation.
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DOI:
10.1167/iovs.16-19465
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发表时间:
2016-09-01
影响因子:
4.4
通讯作者:
Goldberg JL
Goldberg JL
中科院分区:
医学2区
文献类型:
--
作者:
Shaw PX;Fang J;Sang A;Wang Y;Kapiloff MS;Goldberg JL

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我们之前已经证明可溶性腺苷酸环化酶(sAC)是视网膜神经节细胞(RGC)存活和轴突生长所必需的。在此,我们进一步研究了sAC在视网膜发育过程中神经元分化中的作用。Chx10或Math5启动子驱动的Cre-Lox重组用于在视网膜发育过程中有条件地从早期和中期视网膜祖细胞中删除sAC。我们检测了视网膜细胞表达的细胞类型特异性标记物,以估计它们的相对数量,并通过免疫荧光表征成年和新生小鼠的视网膜层状形态。成年Math5cre/sACfl/fl和Chx10cre/sACfl/fl小鼠视网膜神经节细胞和无腺细胞标记物明显低于野生型对照。对RGC发育的影响早在出生后第1天就可以检测到,在表达Math5或chx10的视网膜祖细胞中删除sAC也会减少成年后的神经纤维层厚度。新生Chx10cre/sACfl/fl和Math5cre/sACfl/fl小鼠的光感受器层厚度均有轻微但有统计学意义的下降,而成年Chx10cre/sACfl/fl小鼠的光感受器层厚度的减少和形态的异常持续存在。sAC在RGCs的早期视网膜发育中起重要作用,也在无突细胞和较小程度的光感受器的发育中起重要作用。
We have previously demonstrated that soluble adenylyl cyclase (sAC) is necessary for retinal ganglion cell (RGC) survival and axon growth. Here, we further investigate the role of sAC in neuronal differentiation during retinal development. Chx10 or Math5 promoter-driven Cre-Lox recombination were used to conditionally delete sAC from early and intermediate retinal progenitor cells during retinal development. We examined cell type–specific markers expressed by retinal cells to estimate their relative numbers and characterize retinal laminar morphology by immunofluorescence in adult and newborn mice. Retinal ganglion cell and amacrine cell markers were significantly lower in the retinas of adult Math5cre/sACfl/fl and Chx10cre/sACfl/fl mice than in those of wild-type controls. The effect on RGC development was detectable as early as postnatal day 1 and deleting sAC in either Math5- or Chx10-expressing retinal progenitor cells also reduced nerve fiber layer thickness into adulthood. The thickness of the photoreceptor layer was slightly but statistically significantly decreased in both the newborn Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/fl mice. sAC plays an important role in the early retinal development of RGCs as well as in the development of amacrine cells and to a lesser degree photoreceptors.
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