Department of Ophthalmology, Emory University, Atlanta, Georgia, United States.
The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shan'xi, China.
Invest Ophthalmol Vis Sci. 2021 Jun 1;62(7):9. doi: 10.1167/iovs.62.7.9.
The purpose of this study was to extend our understanding of how aging affects normal retina function and morphology in wild-type C57BL/6J mice, by analyzing electrophysiological recordings and in vivo and post mortem anatomy.
Electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT), and confocal scanning laser ophthalmoscope (cSLO) in vivo images were obtained from mice between the ages of 2 and 32 months in four groups: group 1 (<0.5 years), group 2 (1.0-1.5 years), group 3 (1.5-2.0 years), and group 4 (>2.0 years). Afterward, mouse bodies and eyes were weighed. Eyes were stained with hematoxylin and eosin (H&E) and cell nuclei were quantified.
With aging, mice showed a significant reduction in both a- and b-wave ERG amplitudes in scotopic and photopic conditions. Additionally, total retina and outer nuclear layer (ONL) thickness, as measured by SD-OCT images, were significantly reduced in older groups. The cSLO images showed an increase in auto-fluorescence at the photoreceptor-RPE interface as age increases. H&E cell nuclei quantification showed significant reduction in the ONL in older ages, but no differences in the inner nuclear layer (INL) or ganglion cell layer (GCL).
By using multiple age groups and extending the upper age limit of our animals to approximately 2.65 years (P970), we found that natural aging causes negative effects on retinal function and morphology in a gradual, rather than abrupt, process. Future studies should investigate the exact mechanisms that contribute to these gradual declines in order to discover pathways that could potentially serve as therapeutic targets.
本研究旨在通过分析电生理记录以及体内和死后解剖,扩展我们对正常视网膜功能和形态如何随年龄变化的理解。
在四个组中(<0.5 岁的组 1、1.0-1.5 岁的组 2、1.5-2.0 岁的组 3 和>2.0 岁的组 4),从 2 至 32 月龄的小鼠中获得视网膜电图(ERG)、光谱域光学相干断层扫描(SD-OCT)和共聚焦扫描激光检眼镜(cSLO)的活体图像。之后,对小鼠的身体和眼睛进行称重。用苏木精和伊红(H&E)对眼睛进行染色,并对细胞核进行定量。
随着年龄的增长,在暗适应和明适应条件下,小鼠的 a-和 b-波 ERG 振幅均显著降低。此外,SD-OCT 图像测量的总视网膜和外核层(ONL)厚度在老年组中显著降低。cSLO 图像显示,随着年龄的增长,光感受器-RPE 界面的自发荧光增加。H&E 细胞核定量显示,老年组的 ONL 显著减少,但在 INL 或神经节细胞层(GCL)中没有差异。
通过使用多个年龄组,并将动物的最大年龄上限延长至约 2.65 岁(P970),我们发现,自然衰老对视网膜功能和形态的影响是一个逐渐的过程,而不是突然的。未来的研究应该调查导致这些逐渐下降的确切机制,以便发现可能作为治疗靶点的途径。