Treating amblyopia by digestion of the extracellular matrix and stimulation of axonal growth in the visual cortex

儿童最常见的视觉障碍是弱视（弱视），影响了2-4%的人口。这个项目探索治疗成年弱视的潜在途径。弱视在临床上被定义为：由于儿童时期正常的视觉发育受到一定程度的干扰，尽管进行了最佳的屈光矫正，但视力仍然存在缺陷。弱视通常通过遮挡疗法来治疗（遮盖好眼一段时间以加强弱视眼的使用）。这种方法的有效性随着年龄的增长而降低。迄今为止，在8岁后，即皮层可塑性敏感期结束后，弱视眼是不可能恢复正常视力的。该项目旨在恢复成人视觉皮层的可塑性。我们知道，在成年人的大脑中，神经元形成新连接的能力受到周围分子网的限制，细胞外基质，在青春期变得越来越坚硬。我们计划将酶注入视觉皮层，使基质松弛，并注入其他物质，以促进神经元过程的生长。我们希望这种组合策略能够逆转从被剥夺的眼睛到视觉皮层的功能连接的丧失。我们将采用功能性脑成像来评估视觉皮层对弱视刺激的反应是否会恢复。我们将在动物身上测试和改进我们的治疗方法，然后希望进一步发展这种方法，用于那些因疾病或受伤而失明或视力严重受损的弱视患者。

The commonest visual disorder of children is amblyopia (lazy eye), which affects 2-4% of the population. This project explores potential avenues for treating amblyopia in adulthood.Amblyopia is defined clinically as a deficit in visual acuity despite optimal refractive correction, due to some disruption of normal visual development during childhood. Amblyopia is usually treated by occlusion therapy (covering the good eye for a period of time to enforce the use of the amblyopic eye). The effectiveness of this procedure decreases with age. To date, it is not possible to restore normal vision in an amblyopic eye after the age of 8 years, the end of sensitive period of cortical plasticity. This project aims at restoring visual cortical plasticity in adulthood. We know that in the adult brain, the ability of neurons to form new connections is limited by a mesh of molecules surrounding them, the extracellular matrix, which becomes more and more rigid during adolescence. We plan to infuse enzymes into the visual cortex that will loosen up that matrix, and additional substances that are known to promote the outgrowth of neuronal processes. We hope that this combination strategy will reverse the loss of functional connections from the deprived eye to the visual cortex. We will employ functional brain imaging to assess whether visual cortex responses to stimulation of the amblyopic eye will have returned. We will test and refine our treatment using animals, and later on hope to develop it further for amblyopic patients who have suffered loss of vision in their good eye through illness or injury and have therefore become blind or severely visually impaired.