Sugita Yuko, Yamamoto Haruka, Maeda Yamato, Furukawa Takahisa
Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, Japan.
Front Neurosci. 2020 Dec 1;14:586013. doi: 10.3389/fnins.2020.586013. eCollection 2020.
The decline in visual function due to normal aging impacts various aspects of our daily lives. Previous reports suggest that the aging retina exhibits mislocalization of photoreceptor terminals and reduced amplitudes of scotopic and photopic electroretinogram (ERG) responses in mice. These abnormalities are thought to contribute to age-related visual impairment; however, the extent to which visual function is impaired by aging at the organismal level is unclear. In the present study, we focus on the age-related changes of the optokinetic responses (OKRs) in visual processing. Moreover, we investigated the initial and late phases of the OKRs in young adult (2-3 months old) and aging mice (21-24 months old). The initial phase was evaluated by measuring the open-loop eye velocity of OKRs using sinusoidal grating patterns of various spatial frequencies (SFs) and moving at various temporal frequencies (TFs) for 0.5 s. The aging mice exhibited initial OKRs with a spatiotemporal frequency tuning that was slightly different from those in young adult mice. The late-phase OKRs were investigated by measuring the slow-phase velocity of the optokinetic nystagmus evoked by sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that optimal SF and TF in the normal aging mice are both reduced compared with those in young adult mice. In addition, we measured the OKRs of null ( ) mice, in which mislocalization of photoreceptor terminals is observed even at the young adult stage. We found that the late phase OKR was significantly impaired in mice, which exhibit significantly reduced SF and TF compared with control mice. These OKR abnormalities observed in mice resemble the abnormalities found in normal aging mice. This finding suggests that these mice can be useful mouse models for studying the aging of the retinal tissue and declining visual function. Taken together, the current study demonstrates that normal aging deteriorates to visual motion processing for both the initial and late phases of OKRs. Moreover, it implies that the abnormalities of the visual function in the normal aging mice are at least partly due to mislocalization of photoreceptor synapses.
正常衰老导致的视觉功能下降会影响我们日常生活的各个方面。先前的报告表明,衰老的视网膜在小鼠中表现出光感受器终末的定位错误以及暗视和明视视网膜电图(ERG)反应幅度的降低。这些异常被认为与年龄相关的视力损害有关;然而,在机体水平上衰老对视觉功能的损害程度尚不清楚。在本研究中,我们关注视觉处理中视动反应(OKR)的年龄相关变化。此外,我们研究了年轻成年小鼠(2 - 3个月大)和衰老小鼠(21 - 24个月大)OKR的初始阶段和晚期阶段。通过使用各种空间频率(SF)和以各种时间频率(TF)移动0.5秒的正弦光栅图案来测量OKR的开环眼速度,评估初始阶段。衰老小鼠表现出的初始OKR时空频率调谐与年轻成年小鼠略有不同。通过测量由各种时空频率的正弦光栅移动30秒诱发的视动性眼球震颤的慢相速度来研究晚期OKR。我们发现,与年轻成年小鼠相比,正常衰老小鼠的最佳SF和TF均降低。此外,我们测量了无效( )小鼠的OKR,在这些小鼠中,即使在年轻成年阶段也观察到光感受器终末的定位错误。我们发现, 小鼠的晚期OKR明显受损,与对照小鼠相比,其SF和TF显著降低。在 小鼠中观察到 的这些OKR异常类似于在正常衰老小鼠中发现的异常。这一发现表明,这些小鼠可作为研究视网膜组织衰老和视觉功能下降的有用小鼠模型。综上所述,当前研究表明正常衰老会使OKR的初始阶段和晚期阶段的视觉运动处理能力下降。此外,这意味着正常衰老小鼠视觉功能的异常至少部分是由于光感受器突触的定位错误。