Discipline of Pathology, School of Medical Sciences, Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
PLoS One. 2020 Oct 29;15(10):e0241054. doi: 10.1371/journal.pone.0241054. eCollection 2020.
Toxic metals are suspected to play a role in the pathogenesis of age-related macular degeneration. However, difficulties in detecting the presence of multiple toxic metals within the intact human retina, and in separating primary metal toxicity from the secondary uptake of metals in damaged tissue, have hindered progress in this field. We therefore looked for the presence of several toxic metals in the posterior segment of normal adult eyes using elemental bioimaging.
Paraffin sections of the posterior segment of the eye from seven tissue donors (age range 54-74 years) to an eye bank were examined for toxic metals in situ using laser ablation-inductively coupled plasma-mass spectrometry, a technique that detects multiple elements in tissues, as well as the histochemical technique of autometallography that demonstrates inorganic mercury, silver, and bismuth. No donor had a visual impairment, and no significant retinal abnormalities were seen on post mortem fundoscopy and histology.
Metals found by laser ablation-inductively coupled plasma-mass spectrometry in the retinal pigment epithelium and choriocapillaris were lead (n = 7), nickel (n = 7), iron (n = 7), cadmium (n = 6), mercury (n = 6), bismuth (n = 5), aluminium (n = 3), and silver (n = 1). In the neural retina, mercury was present in six samples, and iron in one. Metals detected in the optic nerve head were iron (N = 7), mercury (N = 7), nickel (N = 4), and aluminium (N = 1). No gold or chromium was seen. Autometallography demonstrated probable inorganic mercury in the retinal pigment epithelium of one donor.
Several toxic metals are taken up by the human retina and optic nerve head. Injury to the retinal pigment epithelium from toxic metals could damage the neuroprotective functions of the retinal pigment epithelium and allow toxic metals to enter the outer neural retina. These findings support the hypothesis that accumulations of toxic metals in the retina could contribute to the pathogenesis of age-related macular degeneration.
有毒金属被怀疑在年龄相关性黄斑变性的发病机制中起作用。然而，由于难以在完整的人视网膜内检测到多种有毒金属的存在，并且难以将主要金属毒性与受损组织中金属的二次摄取区分开来，因此该领域的进展受到了阻碍。因此，我们使用元素生物成像技术在正常成人眼的后节中寻找几种有毒金属的存在。
对来自眼库的 7 位组织供体（年龄范围为 54-74 岁）的眼部后节石蜡切片进行原位检测，使用激光烧蚀-电感耦合等离子体质谱法（一种可检测组织中多种元素的技术）以及组织化学自金属显影技术来检测有毒金属，该技术可显示无机汞、银和铋。没有供体有视力障碍，并且死后眼底检查和组织学检查均未见明显视网膜异常。
通过激光烧蚀-电感耦合等离子体质谱法在视网膜色素上皮和脉络膜毛细血管中发现的金属为铅（n=7）、镍（n=7）、铁（n=7）、镉（n=6）、汞（n=6）、铋（n=5）、铝（n=3）和银（n=1）。在神经视网膜中，有 6 个样本中存在汞，1 个样本中存在铁。在视神经头部检测到的金属为铁（n=7）、汞（n=7）、镍（n=4）和铝（n=1）。未发现金或铬。自金属显影术显示一位供体的视网膜色素上皮中可能存在无机汞。
几种有毒金属被人视网膜和视神经头部吸收。有毒金属对视网膜色素上皮的损伤可能会破坏视网膜色素上皮的神经保护功能，并使有毒金属进入外神经视网膜。这些发现支持了这样的假设，即有毒金属在视网膜中的积累可能导致年龄相关性黄斑变性的发病机制。
