Effects of Blindness on Human Early Visual Pathways

描述(申请人提供)：虽然视觉剥夺的影响已经在动物模型中得到了很好的研究，但关于失明对人类早期视觉通路的影响还知之甚少。了解视觉剥夺对人类早期视觉通路的影响很重要，原因有两个。首先，随着未来几十年出现新的视力恢复程序(如视网膜假体植入、上皮干细胞置换、基因疗法和视网膜移植)，对失明影响的更深入了解将被证明是越来越重要的。第二，外周原因致盲是了解出生前、出生后和成人皮质可塑性的一个很好的模型系统。我们建议结合“最先进的”磁共振成像技术来检查失明对人类皮质下和皮质视觉通路的影响。将比较四个受试组：无眼症(出生时没有眼睛)、非无眼症先天性失明、迟发性失明和正常视力的对照组受试者。高分辨率结构成像将被用来测量由于早期失明导致的外侧膝状体核大小的变化以及V1区大小和髓鞘形成模式的变化。概率纤维束造影术将被用来测量早期失明对外侧膝状核和V1之间以及V1和胼胝体之间联系的影响。磁共振波谱将被用来检测失明对个体内髓鞘形成过程和代谢、胆碱能和GABA能通路的神经化学影响。我们纳入的无眼症、早期失明和晚期失明受试者将使我们能够比较胚胎发育、出生后发育和成人视觉剥夺对人类皮质下和皮质发育的影响。这项工作不仅对了解人类视觉系统的发育具有重要意义，而且对于了解大规模发育的皮质下和皮质可塑性也具有重要意义。

DESCRIPTION (provided by applicant): While the effects of visual deprivation have been well studied in animal models, much less is known about the effects of blindness on human early visual pathways. Understanding the effects of visual deprivation on early visual pathways in humans is important for two reasons. First, a deeper understanding of the effects of blindness will prove increasingly important as new sight restoration procedures (such as retinal prosthetic implants, epithelial stem cell replacements, gene therapies and retinal transplants) become available over the next few decades. Second, blindness due to peripheral causes is an excellent model system for understanding prenatal, postnatal and adult cortical plasticity. We propose to use a combination of "state-of-the-art" MR imaging techniques to examine the effects of blindness on human sub-cortical and cortical visual pathways. Four subject groups will be compared: anophthalmic (born without eyes), non-anophthalmic congenitally blind, late blind and normally sighted control subjects. High resolution structural imaging will be used to measure changes in the size of the lateral geniculate nucleus and changes in the size and myelination patterns of area V1 as a consequence of early blindness. Probabilistic tractography will be used to measure the effects of early blindness on connections between the lateral geniculate nucleus and V1, and between V1 and the corpus callosum. Magnetic resonance spectroscopy will be used to examine the neurochemical effects of blindness on myelination processes and metabolic, cholinergic, and GABA-ergic pathways within blind individuals. Our inclusion of anophthalmic, early blind and late blind subjects will allow us to compare the effects of embryonic development, postnatal development, and adult visual deprivation on sub-cortical and cortical development in humans. This work is likely to have significance not only for understanding development of the human visual system, but also for understanding large-scale developmental sub-cortical and cortical plasticity in general.