Retinal remodeling is a progressive series of negative plasticity revisions that arise from retinal degeneration, and are seen in retinitis pigmentosa, age-related macular degeneration and other forms of retinal disease. These processes occur regardless of the precipitating event leading to degeneration. Retinal remodeling then culminates in a late-stage neurodegeneration that is indistinguishable from progressive central nervous system (CNS) proteinopathies. Following long-term deafferentation from photoreceptor cell death in humans, and long-lived animal models of retinal degeneration, most retinal neurons reprogram, then die. Glial cells reprogram into multiple anomalous metabolic phenotypes. At the same time, survivor neurons display degenerative inclusions that appear identical to progressive CNS neurodegenerative disease, and contain aberrant α-synuclein (α-syn) and phosphorylated α-syn. In addition, ultrastructural analysis indicates a novel potential mechanism for misfolded protein transfer that may explain how proteinopathies spread. While neurodegeneration poses a barrier to prospective retinal interventions that target primary photoreceptor loss, understanding the progression and time-course of retinal remodeling will be essential for the establishment of windows of therapeutic intervention and appropriate tuning and design of interventions. Finally, the development of protein aggregates and widespread neurodegeneration in numerous retinal degenerative diseases positions the retina as a ideal platform for the study of proteinopathies, and mechanisms of neurodegeneration that drive devastating CNS diseases.

视网膜重塑是由视网膜变性引起的一系列渐进的负可塑性修正，见于色素性视网膜炎、年龄相关性黄斑变性和其他形式的视网膜疾病。无论导致退化的突发事件如何，这些过程都会发生。视网膜重塑最终导致晚期神经变性，这种变性与进行性中枢神经系统（CNS）蛋白病无法区分。在人类感光细胞死亡导致长期传入神经阻滞以及视网膜变性的长寿动物模型之后，大多数视网膜神经元会重新编程，然后死亡。神经胶质细胞重编程为多种异常代谢表型。与此同时，幸存者神经元表现出与进行性 CNS 神经退行性疾病相同的退行性包涵体，并含有异常的 α-突触核蛋白 (α-syn) 和磷酸化 α-syn。此外，超微结构分析表明错误折叠蛋白质转移的一种新的潜在机制，可以解释蛋白质病如何传播。虽然神经变性对针对原发性光感受器丧失的前瞻性视网膜干预措施构成了障碍，但了解视网膜重塑的进展和时间过程对于建立治疗干预窗口以及适当调整和设计干预措施至关重要。最后，许多视网膜退行性疾病中蛋白质聚集体的发展和广泛的神经退行性变使视网膜成为研究蛋白质病和导致破坏性中枢神经系统疾病的神经退行性机制的理想平台。