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YuChun Tsai, Bin Lu, Sergey Girman, Clive Svendsen, Robert Cohen, Shaomei Wang; Ocular changes in a rat model of Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6361.
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Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder which is characterized by a progressive decline in learning, memory and executive functions. In addition to cognitive and behavioral deficits, vision disturbances are prevalent in AD patients. Early diagnosis o f AD remains a considerable challenge. Visual symptoms have been reported in early stage of AD, well before the diagnosis is clearly established. Recent studies have highlighted some retinal changes in AD animals, mainly focused on retinal ganglion cell layer. To further investigate the pathologies of ocular abnormalities, a novel AD transgenic rat model was analyzed.
The double transgenic rats were homozygous for mutant APPswe and PS1ΔE9 and were on the inbred Fischer-344 background. Eyes from 14-19 months old transgenic and age-matched control rats were prepared for retinal whole mount and cryostat sections.
The amyloid-β (Aβ) plaques were robustly distributed in hippocampus and cortex but hardly detected in the retina. Compared with age-matched wild type controls, the thickness of choroid was reduced; the retinal pigment epithelial (RPE) cells showed hypertrophy and proliferation; activation of Muller glia cells that increased expression of GFAP was more evidence; clear recruitment of macrophages/microglia to choroid; and upregulation of complement system. Furthermore, there was no significant difference in retinal ganglion cell anterograde transportation and pattern of retinal vessels. Of note, the uneven of photoreceptor loss was found in both wild type and mutant rats.
This study demonstrated that there are abnormal ocular changes in the Alzheimer’s rat model. The changes in the ocular tissue can be visualized in real time with modern imaging technologies, therefore eye can be used as a window to facilitate early diagnosis of AD and monitor therapeutic efficacy.
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