Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice
Author:
Corresponding Author:

Jian Ge. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China. gejian@mail.sysu.edu.cn

Affiliation:

Clc Number:

Fund Project:

Supported by the National Natural Science Foundation of China (No.81430009; No.81400424); the Science and Technology Research and Development Project of Shaanxi Province (No.2014K11-03-07-04).

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    AIM: To identify the pathological role of amyloid beta (Aβ) deposition in retinal degeneration, and explore Aβ deposition on the retinal pigment epithelium cells (RPE) layer and the associated structural and functional changes in Alzheimer’s disease transgenic mice. METHODS: RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic (NTG) mice over 20 months old were examined. Histological changes were investigated via hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) examination, whereas the expression of amyloid precursor protein (APP), Aβ, Zonula occludens-1 (ZO-1) and Ionized calcium binding adaptor molecule-1 (IBA-1) were investigated using immunohistochemistry and immunofluorescence techniques. All of the obtained results were quantitatively and statistically analyzed. RESULTS: In aged transgenic mice, an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice. The RPE demonstrated some vacuole changes, shortened basal infoldings and basal deposition in histopathological examination and TEM tests, wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence. Furthermore, IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch’s membrane (BrM) complex, which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice. The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts. CONCLUSION: The observed Aβ deposition in the RPE layer may cause RPE dysfunction, which is associated with microglia cells infiltration into the retina of aged transgenic mice, suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

    Reference
    Related
    Cited by
Get Citation

Zhi-Zhang Dong, Juan Li, Yi-Feng Gan, et al. Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice. Int J Ophthalmol, 2018,11(5):747-755

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
Publication History
  • Received:September 26,2017
  • Revised:March 21,2018
  • Adopted:
  • Online: May 11,2018
  • Published: