The Accumulation of Aβ Deposits in the Retinas of APPswe/PS1 Transgenic Mice with Retinal Functional Degeneration
Zhizhang Dong1, Juan Li2, Xuerong Sun3, Jian Ge4
1The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
2Department of Ophthalmology, the Fourth Hospital of Xi'an, Xi'an 710004, China
3Institute of Aging, Guangdong Medical University, Dongguan 523000, China
4State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China
Objective: To conduct research on Alzheimer's disease (AD) that is specifically focused on retinal functional and structural changes in TgAPPswePS1 transgenic mice; to demonstrate the role amyloid beta(Aβ) plays in retinal dysfunction; to provide new in sight into retinal AD pathology. Methods: APPswe/PS1 bigenic mice about 24 months of age (experimental group) and non-transgenic littermates about 24 months of age (control group) were grouped for experiments. The eyes of the TgAPPswePS1 mice were examined with electroretinography (ERG). The change in retinal morphology was investigated, while the expressions of the amyloid precursor protein (APP) and Aβ were examined with immunohistochemistry using retinal sections. All of the results were quantified and statistically analyzed by a student's t test. Results: In the experimental group, the rod response, which showed a reduction of the amplitudes of both a and b waves, was compared to the control group. The difference in the b wave amplitude was statistically significant
(t=5.23, P=0.002). For maximum response amplitudes, both flash-triggered a waves and b waves showed a striking decrease compared to the control group. The difference in the a and b waves was statistically significant (t=15.69, 15.76, P<0.001). There were no significant structural abnormalities in the retinal
sections in either the experimental or control groups. We found a decrease in the thickness of the retina in the experimental group compared to the controls, but the the difference was not statistically significant(t=1.85, P=0.087). In the experimental group, APP immunoreactivity was predominantly detected in the
cytoplasm of cells in the ganglion cell layer as well as the inner nuclear layer. By comparison, a much lower staining intensity was observed in the control group in the corresponding regions of the retina. The Aβ accumulation in the retina could be detected by a diffuse pattern and plaque deposits. A majority of
the Aβ-immunoreactive plaques were detected from the ganglion cell layer to the inner plexiform layer, the outer nuclear layer, and even in the photoreceptor outer segment layer. However, no Aβ positive immunoreactivity was detected in the retinas of mice in the control group. Conclusions: Aβ deposits
accumulate in the retina of aged TgAPPswePS1 mice, which is associated with retinal degenerative changes in both function and structure. This suggests that AD-related pathology changes in the retina may contribute to the visual deficits seen in AD.
董志章,李娟,孙雪荣,葛坚. TgAPPswePS1转基因鼠视网膜的功能损伤和Aβ斑块沉积[J]. 中华眼视光学与视觉科学杂志, 2018, 20(1): 46-52.
Zhizhang Dong1, Juan Li2, Xuerong Sun3, Jian Ge4. The Accumulation of Aβ Deposits in the Retinas of APPswe/PS1 Transgenic Mice with Retinal Functional Degeneration. Chinese Journal of Optometry Ophthalmology and Visual science, 2018, 20(1): 46-52. DOI: 10.3760/cma.j.issn.1674-845X.2018.01.009
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