Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

• Authors: Yunchun Tsai, Cedars Sinai Regenerative Medicine Institute; Bin Lu, Cedars Sinai Regenerative Medicine Institute; Alexander V. Ljubimov, Cedars Sinai Regenerative Medicine Institute; Sergey Girman, Cedars Sinai Regenerative Medicine Institute; Fred N. Ross-Cisneros, University of Southern California; Alfredo A. Sadun, University of Southern California; Clive N. Svendsen, Cedars Sinai Regenerative Medicine Institute; Robert Cohen, Emory University; Shaomei Wang, Cedars Sinai Regenerative Medicine Institute
• Journal Title: Investigative Ophthalmology & Visual Science
• Volume: Volume 55, Number 1
• Publisher: AVRO Journals | 2014-01-01, Pages 523-534
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1167/iovs.13-12888
• Subjects: Health Sciences, Opthamology; Engineering, Biomedical; Biology, Neuroscience; Biology, Cell
• Keywords: Science & Technology; Life Sciences & Biomedicine; Ophthalmology; Alzheimer's disease; choroidal thickness; visual acuity; retinal pigment epithelium; Retinal pigment epithelium; Optical coherence tomography; Mild cognitive impairment; Choroidal thickness; Complement activation; Mouse model; Amyloid deposition; Cell changes; Visual impairment; Senile dementia

Abstract

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods: Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. Results As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions: Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus.