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Lining Cao, Fang Wang, Chaoqi Liu, Hao Wang, Jun Yao, Chen Sun; Aβ deposition and senescent RPE cells are found in the retinas of SAMP8 mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):625.
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Our previous study indicated that Aβ-Induced Retinal Pigment Epithelial (RPE) cells senescence may be associated with chronic inflammation in age-related macular degeneration (AMD). The present study was designed to explore whether Aβ deposition and RPE senescence could be found in the senescence-accelerated prone mouse strain 8 (SAMP8), which is an animal model for AMD.
Eyes of both SAMP8 and age-matched SAMR1 (SAM resistant) mice were examined in vivo by fundus photography and electroretinography (ERG). Retinal morphological features were assessed using light and electron microscopy. Aβ deposition and p16-positive senescent RPE cells were traced using immunofluorescence labeling. P16 expression was detected using western blot.
In fundus of SAMP8, Age-dependent increase of drusen-like lesions and the increase of granular autofluorescent spots were respectively detected using IR (near-infrared) and AF (autofluorescence) imaging of confocal scanning laser ophthalmoscope. The amplitude of the ERGs declined with age in SAMP8 and these changes were paralleled with the significant changes in retinal morphological features examined by funduscopy. Histopathological analysis found significant loss of photoreceptor outer segments (OS) and abnormal localization of RPE cells in aged SAMP8 mice. Degenerative changes in RPE cells of aged SAMP8 mice, including massive vacuoles, thickened Bruch’s membrane (BrM), and loss of basal infoldings, were further confirmed by electron microcopy. Increased Aβ deposits in OS layer and p16-positive senescent RPE cells were observed using immunofluorescence microscopy. Western blot confirmed that P16 expression was significantly increased in the RPE cells of aged SAMP8 mice.
Our results showed that aged SAMP8 mice developed ocular pathology similar to some features of human AMD. This AMD mouse model exposed that Aβ deposition and RPE senescence may be associated with AMD development and RPE senescence is likely a mechanistic link between Aβ deposition and inflammation. Further studies, such as subretinal injection of Aβ may help to reveal the critical role and underlying mechanisms of Aβ in the development of AMD.
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