Department of Ophthalmology, University Hospital Bonn, Germany; Division of Ophthalmic Pathology, Department of Ophthalmology, University Hospital Bonn, Germany.
Department of Ophthalmology, University Hospital Bonn, Germany; Division of Ophthalmic Pathology, Department of Ophthalmology, University Hospital Bonn, Germany.
Exp Eye Res. 2022 Apr;217:108958. doi: 10.1016/j.exer.2022.108958. Epub 2022 Jan 24.
The purpose of this study was to investigate Müller cells during the fetal development of the human eye. Müller cells in eyes of 39 human fetuses (11-38 weeks of gestation, WOG) and 6 infants (5 died of abusive head trauma, AHT, aged 1-9 months) were immunohistochemically stained and investigated for spatial and temporal immunoreaction of nestin, CD44, collagen IX and GFAP, which are stem cell markers or markers of intermediate filaments, respectively, in one of the hitherto largest cohorts of fetal eyes. Müller cells could be detected immunohistochemically as early as 12 WOG by immunohistochemical staining with nestin. Nestin was more strongly expressed in Müller cells of the peripheral retina and a centroperipheral gradient of immunoreaction over time was observed. CD44 was predominantly expressed in fetal eyes of the late second and early third trimester between (23 and 27 WOG) and significantly stronger in the infant eyes. Collagen IX labeling in the central retina was significantly stronger than in more peripheral sectors and increased with fetal age. GFAP staining in Müller cells was seen in the eye of a fetus of 38 WOG who died postnatally and in the infant eyes with and without history of AHT. Additionally, GFAP staining was present in the astrocytes of fetal and infant eyes. All examined markers were expressed by Müller cells at different developmental stages highlighting the plasticity of Müller cells during the development of the human eye. GFAP should be cautiously used as a marker for AHT as it was also expressed in fetal astrocytes and Müller cells in eyes without history of AHT.
本研究旨在探讨人眼胚胎发育过程中的 Müller 细胞。通过对 39 个人类胎儿（11-38 孕周，WOG）和 6 名婴儿（5 名死于虐待性头部创伤，AHT，年龄 1-9 个月）的眼球进行免疫组织化学染色，研究了巢蛋白、CD44、胶原 IX 和 GFAP 的时空免疫反应，分别为干细胞标志物或中间丝标志物，这是迄今为止最大的胎儿眼队列之一。早在 12 WOG 时，通过巢蛋白的免疫组织化学染色就可以检测到 Müller 细胞。巢蛋白在周边视网膜的 Müller 细胞中表达更强，并观察到随时间推移的免疫反应从中心到周边的梯度。CD44 在第二和第三个妊娠晚期（23-27 WOG）的胎儿眼中表达明显更强，在婴儿眼中表达更强。中央视网膜的胶原 IX 标记明显强于更周边的区域，并且随胎龄增加而增加。GFAP 在胎龄为 38 WOG 的死后胎儿眼球和有或无 AHT 病史的婴儿眼球的 Müller 细胞中可见染色。此外，GFAP 染色也存在于胎儿和婴儿眼球的星形胶质细胞中。所有检查的标志物在不同的发育阶段均由 Müller 细胞表达，突出了 Müller 细胞在人眼发育过程中的可塑性。GFAP 作为 AHT 的标志物应谨慎使用，因为它也在无 AHT 病史的胎儿和婴儿眼球的星形胶质细胞和 Müller 细胞中表达。
