Laboratory for Cell and Molecular Biology, Department of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, Germany.
Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany.
Cells. 2020 Jan 23;9(2):277. doi: 10.3390/cells9020277.
To investigate whether and how leukemia inhibitory factor (Lif) is involved in mediating the neuroprotective effects of Norrin on retinal ganglion cells (RGC) following excitotoxic damage. Norrin is a secreted protein that protects RGC from methyl-d-aspartate (NMDA)-mediated excitotoxic damage, which is accompanied by increased expression of protective factors such as Lif, Edn2 and Fgf2.
Lif-deficient mice were injected with NMDA in one eye and NMDA plus Norrin into the other eye. RGC damage was investigated and quantified by TUNEL labeling 24 h after injection. Retinal mRNA expression was analyzed by quantitative real-time polymerase chain reaction following retinal treatment.
After intravitreal injection of NMDA and Norrin in wild-type mice approximately 50% less TUNEL positive cells were observed in the RGC layer when compared to NMDA-treated littermates, an effect which was lost in Lif-deficient mice. The mRNA expression for Gfap, a marker for Müller cell gliosis, as well as Edn2 and Fgf2 was induced in wild-type mice following NMDA/Norrin treatment but substantially blocked in Lif-deficient mice.
Norrin mediates its protective properties on RGC via Lif, which is required to enhance Müller cell gliosis and to induce protective factors such as Edn2 or Fgf2.
研究白血病抑制因子（Lif）是否以及如何参与介导诺林对兴奋性损伤后视网膜神经节细胞（RGC）的神经保护作用。诺林是一种分泌蛋白，可防止 RGC 受到甲基-D-天冬氨酸（NMDA）介导的兴奋性损伤，同时还会增加保护因子的表达，如 Lif、Edn2 和 Fgf2。
将 Lif 缺陷型小鼠的一只眼注射 NMDA，另一只眼注射 NMDA 和 Norrin。注射后 24 小时，通过 TUNEL 标记法检测和量化 RGC 损伤。视网膜处理后，通过实时定量聚合酶链反应分析视网膜 mRNA 表达。
在野生型小鼠中，眼内注射 NMDA 和 Norrin 后，与 NMDA 处理的同窝小鼠相比，RGC 层中 TUNEL 阳性细胞减少了约 50%，而在 Lif 缺陷型小鼠中则没有这种作用。NMDA/Norrin 处理后，野生型小鼠的 Gfap（Müller 细胞胶质增生的标志物）、Edn2 和 Fgf2 的 mRNA 表达增加，但在 Lif 缺陷型小鼠中则显著受阻。
诺林通过 Lif 介导其对 RGC 的保护作用，Lif 是增强 Müller 细胞胶质增生和诱导 Edn2 或 Fgf2 等保护因子所必需的。
