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Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):7. doi: 10.1167/iovs.61.3.7.
Cd9 is a tetraspanin membrane protein that plays various roles in tissue development and disease pathogenesis, especially in cancer, but the expression patterns and function of Cd9 in retinal development and disease are not well understood. We asked its roles during retinal photoreceptor degeneration by using CD9-knockout mice.
Cd9 knockout mice and rd1 mice were used to examine roles of Cd9 for progression of photoreceptor degeneration. Reverse transcription-polymerase chain reaction and immunohistochemistry were mainly used as analytical methods.
Cd9 transcripts were only weakly expressed in retina at embryonic day 14, but its expression level subsequently increased and peaked at around postnatal day 12. In 6-week-old female mice derived retina, mRNA expression decreased slightly but was maintained at a significant level. Published RNA-sequencing data and immunohistochemistry indicated that Cd9 was expressed abundantly in Müller glia and weakly in other retinal neurons. Notably, when photoreceptors were damaged, Cd9 expression was increased in rod photoreceptors and decreased in Müller glia. Cd9 knockout mice retinas developed normally; however, once the retina suffered damage, degeneration of photoreceptors was more severe in Cd9 knockout retinas than control retinas. Induction of Edn2, which is known to protect against photoreceptor damage, was severely hampered. In addition, induction of Socs3, which is downstream of gp130 (Il6st), was weaker in Cd9 knockout retinas.
Taken together, these findings indicate that, although Cd9 was dispensable for normal gross morphological development, it protected rod photoreceptors and enhanced Edn2 expression, possibly through modulation of gp130 signaling.
Cd9 是一种四跨膜蛋白，在组织发育和疾病发病机制中发挥着各种作用，尤其是在癌症中，但 Cd9 在视网膜发育和疾病中的表达模式和功能还不太清楚。我们通过使用 CD9 敲除小鼠来研究其在视网膜光感受器变性中的作用。
使用 Cd9 敲除小鼠和 rd1 小鼠来研究 Cd9 对光感受器变性进展的作用。主要采用逆转录聚合酶链反应和免疫组织化学作为分析方法。
Cd9 转录物在胚胎第 14 天的视网膜中仅微弱表达，但随后其表达水平增加，并在出生后第 12 天左右达到峰值。在 6 周龄雌性小鼠来源的视网膜中，mRNA 表达略有下降，但仍保持在显著水平。已发表的 RNA 测序数据和免疫组织化学表明，Cd9 在 Müller 胶质细胞中表达丰富，在其他视网膜神经元中表达较弱。值得注意的是，当光感受器受损时，Cd9 在杆状光感受器中的表达增加，而在 Müller 胶质细胞中的表达减少。Cd9 敲除小鼠的视网膜发育正常；然而，一旦视网膜受到损伤，Cd9 敲除视网膜中的光感受器变性比对照视网膜更为严重。Edn2 的诱导受到严重阻碍，Edn2 已知可保护光感受器免受损伤。此外，Cd9 敲除视网膜中 gp130（Il6st）下游 Socs3 的诱导也较弱。
综上所述，这些发现表明，尽管 Cd9 对于正常的大体形态发育不是必需的，但它可以保护杆状光感受器并增强 Edn2 的表达，这可能是通过调节 gp130 信号通路实现的。
