There is a strong interrelationship between eye and brain diseases. It has been shown that neurodegenerative changes can spread bidirectionally in the visual pathway along neuronal projections. For example, damage to retinal ganglion cells in the retina leads to degeneration of the visual cortex (anterograde degeneration) and vice versa (retrograde degeneration). The underlying mechanisms of this process, known as trans-synaptic degeneration (TSD), are unknown, but TSD contributes to the progression of numerous neurodegenerative disorders, leading to clinical and functional deterioration. The hierarchical structure of the visual system comprises of a strong topographic connectivity between the retina and the visual cortex and therefore serves as an ideal model to study the cellular effect, clinical manifestations, and deterioration extent of TSD. With this review we provide comprehensive information about the neural connectivity, synapse function, molecular changes, and pathophysiology of TSD in visual pathways. We then discuss its bidirectional nature and clinical implications in neurodegenerative diseases. A thorough understanding of TSD in the visual pathway can provide insights into progression of neurodegenerative disorders and its potential as a therapeutic target.

眼部疾病和脑部疾病之间有很强的相互关系。已经表明，神经退行性变化可以沿着神经元投射在视觉通路中双向传播。例如，视网膜中视网膜神经节细胞的损伤会导致视觉皮层退化（顺行退化），反之亦然（逆行退化）。这个过程的潜在机制，称为跨突触变性 (TSD)，尚不清楚，但 TSD 有助于许多神经退行性疾病的进展，导致临床和功能恶化。视觉系统的层次结构包括视网膜和视觉皮层之间的强地形连接，因此是研究 TSD 的细胞效应、临床表现和恶化程度的理想模型。通过这篇综述，我们提供了关于视觉通路中 TSD 的神经连接、突触功能、分子变化和病理生理学的全面信息。然后，我们讨论其在神经退行性疾病中的双向性质和临床意义。对视觉通路中 TSD 的透彻了解可以提供对神经退行性疾病进展及其作为治疗靶点的潜力的见解。