State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlienan Road, Guangzhou, 510060, China.
J Mol Neurosci. 2019 Jul;68(3):465-474. doi: 10.1007/s12031-018-1203-2. Epub 2018 Nov 10.
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been demonstrated to play a crucial part in protecting retinal ganglion cells (RGCs) from apoptosis in various retinal injury animal models. PACAP has two basic groups of receptors: PACAP receptor type 1 (PAC1R) and vasoactive intestinal polypeptide/PACAP receptors (VPAC1R and VPAC2R). However, few studies illustrated the spatial and temporal expression changes of endogenous PACAP and its receptors in a rodent optic nerve crush (ONC) model. In this study, a significant upregulation of PACAP and PAC1R in the retina after ONC was observed in both protein and RNA levels. The peak level of PACAP and PAC1R expression could be found on the fifth day following ONC. In addition, immunofluorescent labeling indicated that PACAP and PAC1R were localized mainly in RGCs. On the contrary, VPAC1R and VPAC2R were hardly detected in the retina. Collectively, the spatiotemporal expression of PACAP and its high-affinity receptor PAC1R were remarkably changed after ONC, and mainly expressed in the ganglion cell layer of the retina. This suggested that the upregulation of PACAP and PAC1R may play a vital role in RGC death after ONC.
垂体腺苷酸环化酶激活肽 (PACAP) 已被证明在各种视网膜损伤动物模型中对保护视网膜神经节细胞 (RGC) 免于凋亡起着至关重要的作用。PACAP 有两种基本的受体群：PACAP 受体 1 (PAC1R) 和血管活性肠肽/PACAP 受体 (VPAC1R 和 VPAC2R)。然而，很少有研究阐明内源性 PACAP 及其受体在啮齿动物视神经挤压 (ONC) 模型中的时空表达变化。在这项研究中，在 ONC 后，无论是在蛋白质水平还是在 RNA 水平，都观察到视网膜中 PACAP 和 PAC1R 的显著上调。PACAP 和 PAC1R 表达的峰值水平可以在 ONC 后第五天找到。此外，免疫荧光标记表明 PACAP 和 PAC1R 主要定位于 RGCs。相反，VPAC1R 和 VPAC2R 在视网膜中几乎检测不到。总之，PACAP 及其高亲和力受体 PAC1R 的时空表达在 ONC 后发生了显著变化，主要表达在视网膜的节细胞层。这表明，PACAP 和 PAC1R 的上调可能在 ONC 后 RGC 死亡中起着重要作用。
