Li Suk-Yee, Yau Suk-Yu, Chen Bai-Yu, Tay David K, Lee Vincent W H, Pu Ming-Liang, Chan Henry H L, So Kwok-Fai
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Cell Mol Neurobiol. 2008 Dec;28(8):1095-107. doi: 10.1007/s10571-008-9286-x. Epub 2008 May 30.
In the present study, we studied the factors that contribute to the injury-resistant property of melanopsin-expressing retinal ganglion cells (mRGCs). Since phosphatidylinositol-3 kinase (PI3 K)/Akt signaling pathway is one of the well-known pathways for neuronal cell survival, we investigated the survival of mRGCs by applying the PI3 K/Akt specific inhibitors after injury. Two injury models, unilateral optic nerve transection and ocular hypertension, were adopted using Sprague-Dawley rats. Inhibitors of PI3 K/Akt were injected intravitreally following injuries to inhibit the PI3 K/Akt signaling pathway. Retinas were dissected after designated survival time, immunohistochemistry was carried out to visualize the mRGCs using melanopsin antibody and the number of mRGCs was counted. Co-expression of melanopsin and phospho-Akt (pAkt) was also examined. Compared to the survival of non-melanopsin-expressing RGCs, mRGCs showed a marked resistance to injury and co-expressed pAkt. Application of PI3 K/Akt inhibitors decreased the survival of mRGCs after injury. Our previous study has shown that mRGC are less susceptible to injury following the induction of ocular hypertension. In this study, we report that mRGCs were injury-resistant to a more severe type of injury, the optic nerve transection. More importantly, the PI3 K/Akt pathway was found to play a role in maintaining the survival of mRGCs after injury.
在本研究中，我们探究了有助于表达黑视蛋白的视网膜神经节细胞（mRGCs）抗损伤特性的因素。由于磷脂酰肌醇-3激酶（PI3K）/Akt信号通路是神经元细胞存活的著名通路之一，我们在损伤后应用PI3K/Akt特异性抑制剂来研究mRGCs的存活情况。使用Sprague-Dawley大鼠采用了两种损伤模型，即单侧视神经横断和高眼压模型。在损伤后经玻璃体内注射PI3K/Akt抑制剂以抑制PI3K/Akt信号通路。在指定的存活时间后解剖视网膜，进行免疫组织化学，用黑视蛋白抗体使mRGCs可视化并计数mRGCs的数量。还检测了黑视蛋白和磷酸化Akt（pAkt）的共表达情况。与不表达黑视蛋白的视网膜神经节细胞的存活情况相比，mRGCs对损伤表现出显著抗性且共表达pAkt。应用PI3K/Akt抑制剂降低了损伤后mRGCs的存活。我们之前的研究表明，高眼压诱导后mRGC对损伤更不敏感。在本研究中，我们报告mRGCs对更严重的损伤类型——视神经横断具有抗损伤能力。更重要的是，发现PI3K/Akt通路在损伤后维持mRGCs的存活中发挥作用。
