Amyloid Beta Deposition Could Cause Corneal Epithelial Cell Degeneration Associated with Increasing Apoptosis in APPswePS1 Transgenic Mice

ABSTRACT

Objective: To investigate the expression of amyloid precursor protein (APP) and amyloid beta (Aβ) in cornea and further explore the pathological and ultrastructural changes in corneal epithelium in APPswePS1 transgenic mice.

Methods: Twelve wild type mice were grouped into control group and twelve TgAPPswePS1 mice at least 8 months old were grouped into the young experiment group (Tg-8M group), and another twelve transgenic mice at least 15 months old were selected into the aged experiment group (Tg-15M group). The pathological degeneration, ultrastructural changes, and the expression of APP, Aβ deposition, and the TUNEL reaction in corneal epithelial cells were observed. Western blot analysis was performed to determine expression levels of APP and Aβ with scraped epithelial debridement. All the results were quantified and analyzed.

Results: In transgenic mice, the H&E-stained cornea sections demonstrated histopathological changes in corneal epithelial cells with irregular arrangement and the number of cell layers decreased, while normal structure observed in controls. In Tg-15M group, the corneal epithelial cell displaced a significant number of intracellular vacuoles with 1–2 cell layers left. Transmission electron microscopy (TEM) further confirmed the dramatic degeneration in corneal epithelium, the microvilli suffered degenerative changes and found with typical fingerpoint-like morphology in controls; however, microspike-like in Tg-15M group, and the number of microvilli decreased considerabely. An APP-positive immunoreaction was detected with a diffuse pattern in the corneal epithelial cells layer, about 3.122 ± 0.596 and 7.372 ± 0.936 fold changes in Tg-8M and Tg-15M groups, respectively, as compared with controls. On corneal flatmount, Aβ deposition found a diffuse pattern in the cytoplasm by fluorescence staining in TgAPPswePS1 with significantly increasing as compared with the controls, but no plaque was found. The apoptosis of TUNEL cells were observed in TgAPPswePS1 mice and increased 16.329 ± 3.542 fold changes in Tg-15M group as compared with controls.

Conclusion: The APP expression and Aβ deposition might cause cornea epithelial cells degeneration in TgAPPswePS1 mice, associated with apoptosis in basal lamina cells.

KEYWORDS:

• Amyloid beta
• apoptosis
• transgenic mice
• corneal epithelium
• Alzheimer’s disease

Declaration of interest

The authors report no conflicts of interest

Additional information

Funding

Grant Information: National Natural Science Foundation of China (No: 81400424); Science and Technology Research and Development Project of Shaanxi Province (2014K11-03-07-04)；Innovative Talents Promotion Project of Shaanxi Province (2017KJXX-87).