Research Laboratories in Ophthalmology, IRCCS-Fondazione Bietti, Rome, Italy.
Laboratory of Developmental Neuroscience and Neural Plasticity, University Campus Bio-Medico, Rome, Italy.
PLoS One. 2019 Feb 27;14(2):e0212732. doi: 10.1371/journal.pone.0212732. eCollection 2019.
A possible link between Nerve Growth Factor (NGF) and Reelin might take place during impaired retinal development occurring in the Reelin deficient mouse model (Reeler). To better characterize NGF and retina impairments at the Reeler retina, vitreous and retina were investigated by means of protein expression and glial cell activation. Reeler (n = 9; RELN-/-) and WT (n = 9; wild-type RELN+/+, B6C3Fe) mice were analyzed at 14, 21 and 28 postnatal days (p). Retinas and vitreous were subjected to confocal analysis and protein array, followed by conventional analysis. A significant increase of NGF, IL33 and TIMP1, a trend to a decrease of IL12 and IL6, as well as a significant decrease of NT3 were detected in Reeler vitreous, particularly at p28 (p<0.05). MIP3β mRNA was decreased while IL33mRNA was significantly upregulated in Reeler retina. Increased number of GFAP+ and Nestin+ cells as well as upregulation of Glutamine Synthetase and Nestin mRNAs were observed in Reeler retinas (p<0.05). These findings extend our previous studies on Reeler retina showing a selective Müller cell activation. NGF and IL33 release into vitreous would suggest a local activation of Müller cells, in addition to retinal ganglion and accessory cells. Overall, the data from this experimental study would strength the potential neuroprotective role played by activated Muller cells through NGF release.
神经生长因子(NGF)和 Reelin 之间可能存在联系,这种联系可能发生在 Reelin 缺陷型小鼠模型(Reeler)中受损的视网膜发育过程中。为了更好地描述 Reeler 视网膜中 NGF 和视网膜损伤,通过蛋白表达和神经胶质细胞激活研究了玻璃体和视网膜。在 14、21 和 28 天龄时(p)分析了 Reeler(n = 9;RELN-/-)和 WT(n = 9;野生型 RELN+/+,B6C3Fe)小鼠。对视网膜和玻璃体进行共聚焦分析和蛋白质阵列分析,然后进行常规分析。在 Reeler 玻璃体中检测到 NGF、IL33 和 TIMP1 的显著增加,IL12 和 IL6 的趋势下降,以及 NT3 的显著下降,特别是在 p28 时(p<0.05)。在 Reeler 视网膜中,MIP3βmRNA 减少,而 IL33mRNA 显著上调。在 Reeler 视网膜中观察到 GFAP+和 Nestin+细胞数量增加以及谷氨酰胺合成酶和 Nestin mRNA 上调(p<0.05)。这些发现扩展了我们之前对 Reeler 视网膜的研究,表明 Müller 细胞的选择性激活。NGF 和 IL33 向玻璃体的释放表明 Müller 细胞的局部激活,除了视网膜神经节和辅助细胞。总的来说,这项实验研究的数据支持了通过释放 NGF 激活 Müller 细胞发挥潜在神经保护作用的假说。