Using the principles of synaptic plasticity to promote recovery from amblyopia

利用突触可塑性原理促进弱视康复

基本信息

批准号：
10231161
负责人：
Mark F Bear
金额：
$ 55.49万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10231161
关键词：
Adult Age Amblyopia Anesthetics Animals Appearance Attention Blindness Brain Characteristics Chemosensitization Clinical Data Depth Perception Development Distant Dose Effectiveness Excitatory Synapse Eye Felis catus Functional disorder Generations Intervention Ketamine Knowledge Laboratories Lateral Geniculate Body Lead Life Local Anesthetics Metaplasia Modification Molecular Motion Mus N-Methyl-D-Aspartate Receptors Neurons Obstruction Outcome Pharmacotherapy Procedures Property Recovery Retina Role Series Synapses Synaptic plasticity Testing Tetrodotoxin Translating Vision Vision Disorders Visual Visual Acuity Visual Cortex Visual system structure Work area striata base deprivation disability early childhood experience experimental study improved infancy monocular deprivation novel novel therapeutic intervention sensory input spatiotemporal standard of care stem

项目摘要

Amblyopia is a prevalent form of visual disability that arises during infancy and early childhood when inputs to the visual cortex from the two eyes are poorly balanced (for example, by misalignment of the eyes, asymmetric refraction, or opacities and obstructions of one eye). Characteristics of amblyopia are very poor acuity in one eye, and an attendant loss of stereopsis. The need for improved treatments for amblyopia is widely acknowledged. Animal studies over the past 50 years have uncovered the pathophysiology of amblyopia. It is well documented that temporary monocular deprivation alters the strength of synapses in primary visual cortex that renders cortical neurons unresponsive to stimulation of the deprived eye. However, much less is known about the mechanisms that serve recovery from amblyopia. We recently discovered that temporarily inactivating the retinas with a local anesthetic sets in motion changes in the brain that enable complete recovery from the effect of early life monocular deprivation when the anesthetic wears off. Our objectives are to uncover the mechanism for how this recovery occurs, and to determine if this knowledge can be translated into new and better treatments for amblyopia.

弱视是一种常见的视觉障碍形式，发生在婴儿期和早期童年时期，两只眼睛对视觉皮层的输入不平衡（例如例如，由于眼睛错位、屈光不对称或混浊，一只眼睛的障碍）。弱视的特点是一只眼睛的视力很差，以及随之而来的立体视觉丧失。需要改进弱视治疗方法得到广泛认可。过去 50 年的动物研究揭示了以下疾病的病理生理学：弱视。有充分证据表明，暂时的单眼剥夺会改变初级视觉皮层突触的强度导致皮层神经元无反应来刺激被剥夺的眼睛。然而，人们对其机制知之甚少有助于弱视康复。我们最近发现暂时失活局部麻醉的视网膜会引起大脑中的运动变化，从而使麻醉后从早年单眼剥夺的影响中完全恢复逐渐消失。我们的目标是揭示这种恢复如何发生的机制，并确定这些知识是否可以转化为新的、更好的治疗方法弱视。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative analysis of structural modifications induced by monocular retinal inactivation and monocular deprivation in the developing cat lateral geniculate nucleus.

发育中的猫外侧膝状核中单眼视网膜失活和单眼剥夺引起的结构修饰的比较分析。

DOI：
发表时间：
2023-08
期刊：
影响因子：
0
作者：
Duffy, Kevin R;Crowder, Nathan A;Heynen, Arnold J;Bear, Mark F
通讯作者：
Bear, Mark F

Recovery from the anatomical effects of long-term monocular deprivation in cat lateral geniculate nucleus.

从猫外侧膝状核长期单眼剥夺的解剖学影响中恢复。

DOI：
发表时间：
2018-02-01
期刊：
影响因子：
0
作者：
Duffy, Kevin R;Fong, Ming;Mitchell, Donald E;Bear, Mark F
通讯作者：
Bear, Mark F

Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.

当健康大脑暴露于麻醉氯胺酮或 60 Hz 光夹带时，小胶质细胞能够使成熟的神经周围网络分解。

DOI：
10.1016/j.celrep.2021.109313
发表时间：
2021-07-06
期刊：
Cell reports
影响因子：
8.8
作者：
Venturino A;Schulz R;De Jesús-Cortés H;Maes ME;Nagy B;Reilly-Andújar F;Colombo G;Cubero RJA;Schoot Uiterkamp FE;Bear MF;Siegert S
通讯作者：
Siegert S