Discipline of Pathology, Sydney Medical School, Brain and Mind Centre, The University of Sydney, Sydney, Australia.
Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, Australia.
PLoS One. 2019 Aug 7;14(8):e0220859. doi: 10.1371/journal.pone.0220859. eCollection 2019.
Damage to the retina and optic nerve is found in some neurodegenerative disorders, but it is unclear whether the optic pathway and central nervous system (CNS) are affected by the same injurious agent, or whether optic pathway damage is due to retrograde degeneration following the CNS damage. Finding an environmental agent that could be responsible for the optic pathway damage would support the hypothesis that this environmental toxicant also triggers the CNS lesions. Toxic metals have been implicated in neurodegenerative disorders, and mercury has been found in the retina and optic nerve of experimentally-exposed animals. Therefore, to see if mercury exposure in the prenatal period could be one link between optic pathway damage and human CNS disorders of later life, we examined the retina and optic nerve of neonatal mice that had been exposed prenatally to mercury vapor, using a technique, autometallography, that detects the presence of mercury within cells. Pregnant mice were exposed to a non-toxic dose of mercury vapor for four hours a day for five days in late gestation, when the mouse placenta most closely resembles the human placenta. The neonatal offspring were sacrificed one day after birth and gapless serial sections of formalin-fixed paraffin-embedded blocks containing the eyes were stained with silver nitrate autometallography to detect inorganic mercury. Mercury was seen in the nuclear membranes of retinal ganglion cells and endothelial cells. A smaller amount of mercury was present in the retinal inner plexiform and inner nuclear layers. Mercury was conspicuous in the peripapillary retinal pigment epithelium. In the optic nerve, mercury was seen in the nuclear membranes and processes of glia and in endothelial cells. Optic pathway and CNS endothelial cells contained mercury. In conclusion, mercury is taken up preferentially by fetal retinal ganglion cells, optic nerve glial cells, the retinal pigment epithelium, and endothelial cells. Mercury induces free radical formation, autoimmunity, and genetic and epigenetic changes, so these findings raise the possibility that mercury plays a part in the pathogenesis of degenerative CNS disorders that also affect the retina and optic nerve.
在一些神经退行性疾病中发现视网膜和视神经损伤,但尚不清楚视神经通路和中枢神经系统(CNS)是否受到相同的损伤因子的影响,或者视神经损伤是否是由于 CNS 损伤后的逆行变性所致。发现一种可能导致视神经通路损伤的环境剂将支持这样一种假说,即这种环境毒物也会引发中枢神经系统病变。有毒金属与神经退行性疾病有关,并且在实验暴露的动物的视网膜和视神经中发现了汞。因此,为了确定在产前暴露于汞是否是视神经通路损伤与人类晚年中枢神经系统疾病之间的一个联系,我们使用一种能够检测细胞内汞存在的技术,自显影术,检查了产前暴露于汞蒸气的新生小鼠的视网膜和视神经。在妊娠晚期,当小鼠胎盘最类似于人胎盘时,每天将怀孕的小鼠暴露于非毒性剂量的汞蒸气中四个小时,持续五天。新生的后代在出生后一天被处死,并对包含眼睛的福尔马林固定石蜡包埋块进行无缝连续切片,用硝酸银自显影术染色以检测无机汞。在视网膜神经节细胞和内皮细胞核膜中可见汞。视网膜内丛状和内核层中存在少量的汞。在视盘周围的视网膜色素上皮中,汞明显可见。在视神经中,在内核膜和胶质细胞以及内皮细胞中可见汞。视神经通路和中枢神经系统的内皮细胞含有汞。总之,汞优先被胎儿视网膜神经节细胞、视神经胶质细胞、视网膜色素上皮和内皮细胞摄取。汞会诱导自由基形成、自身免疫以及遗传和表观遗传变化,因此这些发现提示汞可能在影响视网膜和视神经的退行性中枢神经系统疾病的发病机制中发挥作用。