Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Cell Death Dis. 2018 May 23;9(6):615. doi: 10.1038/s41419-018-0648-0.
Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin α1, α5, β1, β2 and γ1 to be predominantly expressed in Bruch's membrane and the inner limiting membrane. Laminin-332 and laminin γ3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin γ3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin γ3 during human retinogenesis.
层粘连蛋白是细胞外基质的异三聚体糖蛋白。在脊椎动物中已经鉴定出 11 种不同的层粘连蛋白链。它们在人体中广泛表达,具有独特的组织分布。层粘连蛋白在神经视网膜中的表达及其在人类视网膜发生过程中的功能作用尚不清楚。本研究调查了层粘连蛋白在人发育和成年视网膜中的表达,显示层粘连蛋白 α1、α5、β1、β2 和 γ1 主要在布鲁赫膜和内界膜中表达。层粘连蛋白-332 和层粘连蛋白 γ3 的表达在视网膜发生过程中主要观察到在神经视网膜中。这些表达模式在多能干细胞衍生的视网膜类器官中基本保持不变。在视网膜类器官中阻断层粘连蛋白 γ3 的功能会导致层状结构和突触形成中断、光感受器组织和视网膜神经节细胞丧失。我们的数据表明层粘连蛋白具有独特的时空表达,并揭示了层粘连蛋白 γ3 在人类视网膜发生过程中的新作用。