Restoration of retinal structure and function after selective photocoagulation of

选择性光凝术后视网膜结构和功能的恢复

• 批准号: 8990485
• 负责人: Alexander Sher
• 金额: $ 50.82万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8990485
• 关键词: Adult; Adverse effects; Affect; Antibodies; Area; Blindness; Cells; Cessation of life; Cicatrix; Clinical; Color Perception; Cone; Data; Development; Disease; Electrodes; Goals; Healed; Health; Histology; Injury; Label; Lasers; Left; Lesion; Light Coagulation; Measurement; Measures; Modeling; Neurons; Oryctolagus cuniculus; Pathway interactions; Patients; Pattern; Perception; Photoreceptors; Process; Property; Research; Retina; Retinal; Retinal Diseases; Retinal Ganglion Cells; Retinal blind spot; Rodent; Scotoma; Shapes; Site; Specificity; Spermophilus; Stem cell transplant; Stem cells; Structure; Synapses; Testing; Time; Transplantation; Vertebrate Photoreceptors; Vision; Visual; cell type; functional restoration; ganglion cell; healing; insight; laser photocoagulation; migration; multi-electrode arrays; novel strategies; postsynaptic; receptive field; repaired; research study; response; restoration; retinal neuron; standard of care; synaptogenesis; visual stimulus

DESCRIPTION (provided by applicant): In the retina, death of photoreceptors due to injury or disease leads to irreversible loss of vision. Loss of photoreceptors is often followed by destructive remodeling of the inner retinal layers that leads to abnormal retinal structure and function. Recently, it has been discovered that selective destruction of a small patch of photoreceptors leaving the inner-retinal neurons intact, leads to migration of the photoreceptors from outside of the lesioned area into the lesion over the period of a few months, thereby restoring retinal continuity. Our pilot data shows that as a result of this process retinal sensitiity in the initial blind spot introduced by photocoagulation can be restored. Moreover, our observations indicate that migrating photoreceptors establish new synaptic connections with bipolar cells in the lesion. These findings demonstrate that retina has the potential for constructive plasticity never observed or even suspected before. Our goal is to establish the mechanism and the limits of this new exciting phenomenon. In particular, the main hypothesis we propose to test is that the healthy photoreceptors migrate inside the lesion and establish new and appropriate connections to the deafferented retinal circuitry inside the lesion. We will test this hypothesis by characterizing functional and anatomical changes induced by selective photocoagulation through multielectrode array recordings of retinal activity and antibody labeling of various retinal neuronal types and synapses. The phenomenon of the constructive retinal plasticity becomes an extremely useful model for understanding the mechanisms of the development of the intricate and specific retinal connectivity in the adult mammalian retina. Of immediate clinical importance is that the results of the proposed research will enable development of novel approach to retinal photocoagulation that will avoid deleterious side effects of the current standard of care, such as scotomata and scarring. Retinal photocoagulation is widely used to treat various retinopathies and its improvement will affect millions of patients worldwide. Results of the research may also provide insights into processes of functional integration of transplanted photoreceptors or stem cells into the adult retina.

描述（由申请人提供）：在视网膜中，由于损伤或疾病导致的光感受器死亡导致不可逆的视力丧失。光感受器的丧失通常伴随着视网膜内层的破坏性重塑，导致视网膜结构和功能异常。最近，研究人员发现，选择性地破坏一小块光感受器，使视网膜内神经元完好无损，导致光感受器在几个月的时间内从病变区域外迁移到病变区域，从而恢复视网膜的连续性。我们的试验数据表明，由于这个过程的视网膜灵敏度在最初的盲点引入光凝可以恢复。此外，我们的观察表明，迁移的光感受器与病变中的双极细胞建立了新的突触连接。这些发现表明，视网膜具有以前从未观察到甚至怀疑过的建设性可塑性的潜力。我们的目标是建立这一令人兴奋的新现象的机制和限制。特别是，我们提出的主要假设是，健康的光感受器在病变内迁移，并与病变内失传入的视网膜回路建立新的和适当的连接。我们将通过多电极阵列记录视网膜活动和各种视网膜神经元类型和突触的抗体标记，通过表征选择性光凝诱导的功能和解剖变化来验证这一假设。构建性视网膜可塑性现象为理解成年哺乳动物视网膜复杂而特异的视网膜连接发育机制提供了一个非常有用的模型。具有直接临床重要性的是，所提出的研究结果将使视网膜光凝治疗的新方法得以发展，从而避免当前治疗标准的有害副作用，如暗斑和疤痕。视网膜光凝术被广泛用于治疗各种视网膜病变，其改善将影响全球数百万患者。该研究结果也可能为移植的光感受器或干细胞进入成人视网膜的功能整合过程提供见解。