Abstract
Purpose::
The senescence-accelerated mouse (SAM) is a common model used in human aging research but the aging process of the SAM’s retina has yet to be elucidated. In the present study, the retinal aging properties of SAM were characterized. We aim to elucidate the SAM as a possible aging model for eye research.
Methods::
The rare inbred strain of SAM (SAMP8), a sister control strain (SAMR1) and an unrelated normal strain (ICR) were used and mice of different ages (3, 6 and 9 months) were sacrificed. Scanning electron microscopy was employed to investigate the retinal changes. Immunohistochemical method was adopted to study the biochemical variation, namely the expression of proliferation cell nuclear antigen (PCNA) and superoxide dismutase (SOD), in the retinal layers. The TUNEL analysis was carried out to determine retinal cell death during the aging process.
Results::
Morphological study by scanning electron microscopy showed that the degree of degeneration (e.g. outer segment dilation, malformation and dystrophy) was greatest in SAMR1. Blebs were formed on the membrane surface of photoreceptors, which were particularly obvious in the SAMR1 at 9 months of age. The photoreceptors of ICR remained intact and only minor dystrophy was seen at a later stage. By using the TUNEL technique, most severe cell death was seen in the outer nuclear layer (ONL) and the inner nuclear layer (INL) among different age groups and strains. The retinal layers of SAMP8 showed a higher amount of TUNEL nuclei than others of a similar age. On the other hand, the retina of SAMR1 (9 months) showed the highest oxidative level (as revealed by SOD staining) with major positive sites observed at the INL and minor positive sites at both the retinal pigmented epithelium and ganglion cell layers. Besides, cell proliferative ability decreased with age in all strains with the weakest proliferative ability observed in the SAMP8 as determined by the PCNA signals. It has yet to be clarified whether these proliferative cells are glial cells.
Conclusions::
Our study showed that the retinae of both the SAMP8 and SAMR1 demonstrated accelerated-aging characteristics. It was noted that although SAMR1 was commonly employed as the control for SAMP strains in aging studies, it has also demonstrated significant signs of ocular aging as SAMP, when compared with normal mice (e.g. ICR). Therefore, the SAM strains could be a useful model for ocular aging research, yet a careful selection of a normal mouse would be necessary for comparison.
Keywords: aging • retina • retinal degenerations: cell biology