PDF(Pubmed)
Abstract：
UNASSIGNED: High altitude retinopathy (HAR) is a retinal functional disorder caused by inadequate adaptation after exposure to high altitude. However, the cellular and molecular mechanisms underlying retinal dysfunction remain elusive. Retinal ganglion cell (RGC) injury is the most important pathological basis for most retinal and optic nerve diseases. Studies focusing on RGC injury after high-altitude exposure (HAE) are scanty. Therefore, the present study sought to explore both functional and morphological alterations of RGCs after HAE.
UNASSIGNED: A mouse model of acute hypobaric hypoxia was established by mimicking the conditions of a high altitude of 5000 m. After HAE for 2, 4, 6, 10, 24, and 72 hours, the functional and morphological alterations of RGCs were assessed using retinal hematoxylin and eosin (H&E) sections, retinal whole mounts, transmission electron microscopy (TEM), and the photopic negative response (PhNR) of the electroretinogram.
UNASSIGNED: Compared with the control group, the thickness of the ganglion cell layer and retinal nerve fiber layer increased significantly, RGC loss remained significant, and the amplitudes of a-wave, b-wave, and PhNR were significantly reduced after HAE. In addition, RGCs and their axons exhibited an abnormal ultrastructure after HAE, including nuclear membrane abnormalities, uneven distribution of chromatin in the nucleus, decreased cytoplasmic electron density, widening and vacuolization of the gap between axons, loosening and disorder of myelin sheath structure, widening of the gap between myelin sheath and axon membrane, decreased axoplasmic density, unclear microtubule and nerve fiber structure, and abnormal mitochondrial structure (mostly swollen, with widened membrane gaps and reduced cristae and vacuolization).
UNASSIGNED: The study findings confirm that the morphology and function of RGCs are damaged after HAE. These findings lay the foundation for further study of the specific molecular mechanisms of HAR and promote the effective prevention.
UNASSIGNED: A mouse model of acute hypobaric hypoxia was established by mimicking the conditions of a high altitude of 5000 m. After HAE for 2, 4, 6, 10, 24, and 72 hours, the functional and morphological alterations of RGCs were assessed using retinal hematoxylin and eosin (H&E) sections, retinal whole mounts, transmission electron microscopy (TEM), and the photopic negative response (PhNR) of the electroretinogram.
UNASSIGNED: Compared with the control group, the thickness of the ganglion cell layer and retinal nerve fiber layer increased significantly, RGC loss remained significant, and the amplitudes of a-wave, b-wave, and PhNR were significantly reduced after HAE. In addition, RGCs and their axons exhibited an abnormal ultrastructure after HAE, including nuclear membrane abnormalities, uneven distribution of chromatin in the nucleus, decreased cytoplasmic electron density, widening and vacuolization of the gap between axons, loosening and disorder of myelin sheath structure, widening of the gap between myelin sheath and axon membrane, decreased axoplasmic density, unclear microtubule and nerve fiber structure, and abnormal mitochondrial structure (mostly swollen, with widened membrane gaps and reduced cristae and vacuolization).
UNASSIGNED: The study findings confirm that the morphology and function of RGCs are damaged after HAE. These findings lay the foundation for further study of the specific molecular mechanisms of HAR and promote the effective prevention.
摘要：
■高海拔视网膜病变（HAR）是由于暴露于高海拔地区后适应不足而引起的视网膜功能障碍。然而,视网膜功能障碍的细胞和分子机制仍然难以捉摸。视网膜神经节细胞（RGC）损伤是大多数视网膜和视神经疾病的最重要病理基础。针对高原暴露（HAE）后RGC损伤的研究很少。因此,本研究试图探索HAE后RGC的功能和形态改变。
■通过模拟5000m的高海拔条件，建立了急性低压缺氧的小鼠模型。HAE后2、4、6、10、24和72小时，使用视网膜苏木精和曙红（H&E）切片评估RGC的功能和形态改变，视网膜整体坐骑，透射电子显微镜（TEM），和视网膜电图的明视负反应（PhNR）。
■与对照组相比，神经节细胞层和视网膜神经纤维层厚度明显增加,RGC损失仍然很大，以及a波的振幅，b波,HAE后PhNR显著降低。此外,HAE后RGC及其轴突表现出异常的超微结构，包括核膜异常,染色质在细胞核中分布不均,细胞质电子密度降低，轴突之间的间隙扩大和空泡化，髓鞘结构松动和紊乱，扩大髓鞘和轴突膜之间的间隙，轴质密度降低，不清楚的微管和神经纤维结构，和异常的线粒体结构（主要是肿胀，膜间隙扩大，cr和空泡减少）。
■研究结果证实，HAE后RGC的形态和功能受到损害。这些发现为进一步研究HAR的具体分子机制和促进有效预防奠定了基础。
■通过模拟5000m的高海拔条件，建立了急性低压缺氧的小鼠模型。HAE后2、4、6、10、24和72小时，使用视网膜苏木精和曙红（H&E）切片评估RGC的功能和形态改变，视网膜整体坐骑，透射电子显微镜（TEM），和视网膜电图的明视负反应（PhNR）。
■与对照组相比，神经节细胞层和视网膜神经纤维层厚度明显增加,RGC损失仍然很大，以及a波的振幅，b波,HAE后PhNR显著降低。此外,HAE后RGC及其轴突表现出异常的超微结构，包括核膜异常,染色质在细胞核中分布不均,细胞质电子密度降低，轴突之间的间隙扩大和空泡化，髓鞘结构松动和紊乱，扩大髓鞘和轴突膜之间的间隙，轴质密度降低，不清楚的微管和神经纤维结构，和异常的线粒体结构（主要是肿胀，膜间隙扩大，cr和空泡减少）。
■研究结果证实，HAE后RGC的形态和功能受到损害。这些发现为进一步研究HAR的具体分子机制和促进有效预防奠定了基础。
