Effects of Blindness on Human Early Visual Pathways

描述（由申请人提供）：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，但对失明对人类早期视觉通路的影响知之甚少。了解视觉剥夺对人类早期视觉通路的影响有两个重要原因。首先，随着新的视力恢复方法（如视网膜假体植入、上皮干细胞替代、基因疗法和视网膜移植）在未来几十年变得可行，对失明影响的更深入理解将变得越来越重要。其次，由于外周原因导致的失明是理解产前、产后和成人皮质可塑性的一个很好的模型系统。我们建议结合使用“最先进的”MR成像技术来检查失明对人类皮层下和皮层视觉通路的影响。将四组受试者进行比较：无眼（天生无眼）、非无眼先天性失明、晚期失明和正常视力对照组。高分辨率结构成像将用于测量外侧膝状核大小的变化以及V1区大小和髓鞘形成模式的变化，这是早期失明的结果。概率神经束造影将用于测量早期失明对外侧膝状核与V1之间以及V1与胼胝体之间连接的影响。磁共振波谱将用于检查失明对盲人体内髓鞘形成过程和代谢、胆碱能和氨基丁酸能通路的神经化学影响。我们纳入无眼、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层下和皮层发育的影响。这项工作可能不仅对理解人类视觉系统的发育具有重要意义，而且对理解大尺度的皮层下发育和皮层可塑性具有重要意义。

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.