Development of a small molecule combinatorial treatment for RGC survival and axon regeneration to restore sight after optic neuropathy

开发针对 RGC 存活和轴突再生的小分子组合疗法，以恢复视神经病变后的视力

• 批准号: MR/J011584/1
• 负责人: Peter Morgan-Warren
• 金额: $ 27.69万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ011584%2F1
• 关键词: Development; small; molecule; combinatorial; treatment

We plan to investigate the possibility of developing a new molecular treatment to promote the regeneration of nerves in the visual system following damage to the optic nerves. The optic nerve connects the eye to the brain and is essential for providing signals about visual stimuli for the brain to interpret as images. There are several conditions in which the optic nerve is damaged, including glaucoma, ischaemic damage and following head/eye traumatic injury. These conditions cause severe visual impairment and are common causes of blindness. Once optic nerve damage has taken place, the nerve cells die and there are currently no treatments available that can reverse the process and restore vision.Recent laboratory research models suggest that there are molecular mechanisms that can be manipulated in order to promote the survival and regeneration of nerve tissue following disease or injury. It may also be possible to restore connections to the brain that are lost in the disease process. The research to be undertaken at the Department of Clinical and Experimental Medicine at the University of Birmingham aims to examine this in more detail and develop a new molecular treatment in order to protect and regenerate nerves and restore visual function. To investigate this we will construct a new molecule that acts in combination with others already shown to influence the nerve regeneration mechanisms. This will then be investigated in an animal model to assess whether nerve cells are able to survive and regenerate as we hypothesise, and then undertake further experiments to assess whether regeneration of nerve cells enables the restoration of visual function.Through this research we hope to show that optic nerve tissue can be regenerated following disease/injury and that visual function can be restored. This may then be translated into new therapies and offer hope for patients who have lost vision from optic nerve conditions.

我们计划研究开发一种新的分子治疗方法来促进视神经损伤后视觉系统神经再生的可能性。视神经连接眼睛和大脑，并且对于提供关于视觉刺激的信号以使大脑解释为图像是必不可少的。有几种视神经受损的情况，包括青光眼、缺血性损伤和随后的头部/眼睛创伤性损伤。这些情况会导致严重的视力障碍，是失明的常见原因。一旦视神经损伤发生，神经细胞死亡，目前还没有可用的治疗方法可以逆转这一过程并恢复视力。最近的实验室研究模型表明，有一些分子机制可以被操纵，以促进疾病或损伤后神经组织的存活和再生。它也有可能恢复在疾病过程中失去的与大脑的连接。伯明翰大学临床和实验医学系将进行的研究旨在更详细地研究这一点，并开发新的分子治疗方法，以保护和再生神经并恢复视觉功能。为了研究这一点，我们将构建一种新的分子，该分子与其他已经显示出影响神经再生机制的分子相结合。我们将在动物模型中进行研究，以评估神经细胞是否能够存活和再生，然后进行进一步的实验，以评估神经细胞的再生是否能够恢复视觉功能。通过这项研究，我们希望表明视神经组织在疾病/损伤后可以再生，视觉功能可以恢复。这可能会转化为新的疗法，并为因视神经疾病而失去视力的患者带来希望。

项目成果

Non-viral-mediated suppression of AMIGO3 promotes disinhibited NT3-mediated regeneration of spinal cord dorsal column axons.

• DOI: 10.1038/s41598-018-29124-z
• 发表时间: 2018-07-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Almutiri S;Berry M;Logan A;Ahmed Z
• 通讯作者: Ahmed Z

Corrigendum to "Prospects for mTOR-mediated functional repair after central nervous system trauma" [Neurobiol. Dis. 85 (2016) 99-110].

“中枢神经系统创伤后 mTOR 介导的功能修复的前景”的勘误 [Neurobiol。

• DOI: 10.1016/j.nbd.2016.12.001
• 发表时间: 2017
• 期刊: Neurobiology of disease
• 影响因子: 6.1
• 作者: Berry M

LINGO-1 and AMIGO3, potential therapeutic targets for neurological and dysmyelinating disorders?

• DOI: 10.4103/1673-5374.213538
• 发表时间: 2017-08
• 期刊: Neural regeneration research
• 影响因子: 6.1
• 作者: Foale S;Berry M;Logan A;Fulton D;Ahmed Z
• 通讯作者: Ahmed Z

Salivary MicroRNAs: Diagnostic Markers of Mild Traumatic Brain Injury in Contact-Sport.

• DOI: 10.3389/fnmol.2018.00290
• 发表时间: 2018
• 期刊: Frontiers in molecular neuroscience
• 影响因子: 4.8
• 作者: Di Pietro V;Porto E;Ragusa M;Barbagallo C;Davies D;Forcione M;Logan A;Di Pietro C;Purrello M;Grey M;Hammond D;Sawlani V;Barbey AK;Belli A
• 通讯作者: Belli A