iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Biomolecules. 2023 Jan 15;13(1):180. doi: 10.3390/biom13010180.
Alpha-synuclein (aSyn) plays a central role in Parkinson's disease (PD) and has been extensively studied in the brain. This protein is part of the synuclein family, which is also composed of beta-synuclein (bSyn) and gamma-synuclein (gSyn). In addition to its neurotoxic role, synucleins have important functions in the nervous system, modulating synaptic transmission. Synucleins are expressed in the retina, but they have been poorly characterized. However, there is evidence that they are important for visual function and that they can play a role in retinal degeneration. This study aimed to profile synucleins in the retina of naturally aged mice and to correlate their patterns with specific retinal cells. With aging, we observed a decrease in the thickness of specific retinal layers, accompanied by an increase in glial reactivity. Moreover, the aSyn levels decreased, whereas bSyn increased with aging. The colocalization of both proteins was decreased in the inner plexiform layer (IPL) of the aged retina. gSyn presented an age-related decrease at the inner nuclear layer but was not significantly changed in the ganglion cell layer. The synaptic marker synaptophysin was shown to be preferentially colocalized with aSyn in the IPL with aging. At the same time, aSyn was found to exist at the presynaptic endings of bipolar cells and was affected by aging. Overall, this study suggests that physiological aging can be responsible for changes in the retinal tissue, implicating functional alterations that could affect synuclein family function.
α-突触核蛋白（aSyn）在帕金森病（PD）中起核心作用，并在大脑中得到了广泛研究。该蛋白是突触核蛋白家族的一部分，该家族还包括β-突触核蛋白（bSyn）和γ-突触核蛋白（gSyn）。除了其神经毒性作用外，突触核蛋白在神经系统中具有重要功能，调节突触传递。突触核蛋白在视网膜中表达，但它们的特征描述较差。然而，有证据表明它们对视觉功能很重要，并且可能在视网膜变性中发挥作用。本研究旨在描绘自然衰老小鼠视网膜中的突触核蛋白，并将其模式与特定的视网膜细胞相关联。随着年龄的增长，我们观察到特定视网膜层的厚度减少，同时胶质细胞反应性增加。此外，aSyn 水平随着年龄的增长而降低，而 bSyn 则增加。两种蛋白质在衰老视网膜的内丛状层（IPL）中的共定位减少。gSyn 在核内层中与年龄相关地减少，但在节细胞层中没有明显变化。突触标志物突触小泡蛋白随着年龄的增长在 IPL 中与 aSyn 优先共定位。同时，发现 aSyn 存在于双极细胞的突触前末端，并受衰老影响。总的来说，这项研究表明，生理衰老可能导致视网膜组织发生变化，暗示功能改变可能影响突触核蛋白家族的功能。
