Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Complutense University of Madrid, c/Arcos de Jalón 118, E-28037, Madrid, Spain.
Laboratory of Experimental Ophthalmology, Dept. of Ophthalmology, Faculty of Medicine, University of Murcia and Murcia Institute of Bio-Health Research (IMIB), E-30120, El Palmar, Murcia, Spain.
Brain Res Bull. 2019 Aug;150:61-74. doi: 10.1016/j.brainresbull.2019.05.006. Epub 2019 May 16.
Glaucoma is a common cause of visual impairment and blindness, characterized by retinal ganglion cell (RGC) death. The mechanisms that trigger the development of glaucoma remain unknown and have gained significant relevance in the study of this neurodegenerative disease. P2X7 purinergic receptors (P2X7R) could be involved in the regulation of the synaptic transmission and neuronal death in the retina through different pathways. The aim of this study was to characterize the molecular signals underlying glaucomatous retinal injury. The time-course of functional, morphological, and molecular changes in the glaucomatous retina of the DBA/2J mice were investigated. The expression and localization of P2X7R was analysed in relation with retinal markers. Caspase-3, JNK, and p38 were evaluated in control and glaucomatous mice by immunohistochemical and western-blot analysis. Furthermore, electroretinogram recordings (ERG) were performed to assess inner retina dysfunction. Glaucomatous mice exhibited changes in P2X7R expression as long as the pathology progressed. There was P2X7R overexpression in RGCs, the primary injured neurons, which correlated with the loss of function through ERG measurements. All analyzed MAPK and caspase-3 proteins were upregulated in the DBA/2J retinas suggesting a pro-apoptotic cell death. The increase in P2X7Rs presence may contribute, together with other factors, to the changes in retinal functionality and the concomitant death of RGCs. These findings provide evidence of possible intracellular pathways responsible for apoptosis regulation during glaucomatous degeneration.
青光眼是一种常见的致盲眼病，其特征是视网膜神经节细胞（RGC）死亡。引发青光眼发展的机制尚不清楚，在研究这种神经退行性疾病时具有重要意义。P2X7 嘌呤能受体（P2X7R）可能通过不同途径参与调节视网膜中的突触传递和神经元死亡。本研究旨在描述青光眼视网膜损伤的分子信号。研究了 DBA/2J 小鼠青光眼视网膜的功能、形态和分子变化的时程。分析了 P2X7R 的表达和定位与视网膜标志物的关系。通过免疫组织化学和 Western blot 分析评估了对照和青光眼小鼠中的 caspase-3、JNK 和 p38。此外，还进行了视网膜电图（ERG）记录以评估内视网膜功能障碍。只要病理进展，青光眼小鼠就会发生 P2X7R 表达变化。在原发性损伤神经元 RGC 中存在 P2X7R 过表达，这与通过 ERG 测量的功能丧失有关。在 DBA/2J 视网膜中分析的所有 MAPK 和 caspase-3 蛋白均上调，表明存在促凋亡细胞死亡。P2X7Rs 存在的增加可能与其他因素一起，导致视网膜功能的变化和 RGC 的同时死亡。这些发现为青光眼变性过程中细胞凋亡调节的可能细胞内途径提供了证据。
