Hoffmann Michael B, Thieme Hagen, Liedecke Karin, Meltendorf Synke, Zenker Martin, Wieland Ilse
Department of Ophthalmology Otto-von-Guericke-University, Magdeburg, Germany 2Center for Behavioural Brain Sciences, Magdeburg, Germany.
Department of Ophthalmology Otto-von-Guericke-University, Magdeburg, Germany.
Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7427-37. doi: 10.1167/iovs.15-17705.
Numerous animal studies demonstrated the importance of components of the ephrin/Eph system for correct visual system development. Analogous investigations in humans are entirely missing. Here, we examined the visual system in humans with ephrin-B1 deficiency, which is x-linked and associated with the cranio-fronto-nasal syndrome (CFNS) in heterozygous females.
For one male hemizygous for ephrin-B1 deficiency and three affected heterozygous females with molecular-genetically confirmed mutations, the integrity of the partial decussation of the optic nerves was assessed with visual evoked potentials (VEPs) and compared with albinotic, achiasmic, and control participants with healthy vision. Further, retinal morphology and function and the gross-retinotopic representation of the primary visual cortex were examined with spectral-domain optical coherence tomography (SD-OCT), ERG, and multifocal (mf) VEPs for the male participant and part of the carriers.
Strabismus and lack of stereovision was evident in the male and two of the females. Other characteristics of the visual system organization and function were normal: (1) retina: SD-OCT and funduscopy indicated normal foveal and optic nerve head morphology. Electroretinograms indicated normal retinal function, (2) optic chiasm: conventional (c)VEP showed no evidence for misrouting and mfVEPs were only suggestive of, if any, very minor local misrouting, and (3) visual cortex: mfVEP characteristics indicated normal retinotopic gross-representations of the contralateral visual hemifield in each hemisphere.
While ephrin-B1 deficiency leads to abnormal visual pathways in mice, it leaves the human visual system, apart from deficits in binocular vision, largely normal. We presume that other components of the ephrin-system can substitute the lack of ephrin-B1 in humans.
众多动物研究表明， Ephrin/Eph 系统的组成部分对视觉系统的正常发育至关重要。然而，目前完全缺乏针对人类的类似研究。在此，我们对患有 Ephrin-B1 缺乏症的人类视觉系统进行了研究，该缺乏症为 X 连锁，杂合子女性患者会伴有颅额鼻综合征（CFNS）。
对于一名 Ephrin-B1 缺乏症的半合子男性以及三名经分子遗传学证实存在突变的受影响杂合子女性，通过视觉诱发电位（VEP）评估视神经部分交叉的完整性，并与白化病、无交叉以及视力正常的对照参与者进行比较。此外，还对该男性参与者和部分携带者进行了光谱域光学相干断层扫描（SD-OCT）、视网膜电图（ERG）以及多焦点（mf）VEP 检查，以观察视网膜形态和功能以及初级视觉皮层的大致视网膜拓扑表征。
该男性和两名女性均出现斜视且缺乏立体视觉。视觉系统组织和功能的其他特征均正常：（1）视网膜：SD-OCT 和眼底检查显示中央凹和视神经乳头形态正常。视网膜电图表明视网膜功能正常；（2）视交叉：传统（c）VEP 未显示神经纤维走行异常的证据，mfVEP 仅提示存在极轻微的局部神经纤维走行异常；（3）视觉皮层：mfVEP 特征表明每个半球对侧视觉半野的视网膜拓扑大致表征正常。
虽然 Ephrin-B1 缺乏会导致小鼠视觉通路异常，但除了双眼视觉缺陷外，人类视觉系统在很大程度上仍保持正常。我们推测 Ephrin 系统的其他组成部分可以替代人类中 Ephrin-B1 的缺乏。
