Author:
Dong Zhizhang,Li Juan,Leng Yunxia,Sun Xuerong,Hu Huiling,He Yuan,Tan Zhiqun,Ge Jian
Abstract
Abstract
Background
Intensive light exposure and beta-amyloid (Aβ) aggregates have been known as a risk factor for macular degeneration and an important component in the pathologic drusen structure involved in this disorder, respectively. However, it is unknown whether Aβ deposition mediates or exacerbates light exposure-induced pathogenesis of macular degeneration. Several studies including the one from us already showed accumulation of Aβ deposits in the retina in Alzheimer's transgenic mice. Using histopathological analysis combined with electroretinographic functional assessment, we investigated the effects of cyclic intensive light exposure (CILE) on the architecture of retina and related function in the APPswe/PS1bigenic mouse.
Results
Histopathological analysis has found significant loss of outer nuclear layer/photoreceptor outer segment and outer plexiform layer along with abnormal hypo- and hyper-pigmentation in the retinal pigment epithelium (RPE), remarkable choroidal neovascularization (CNV), and exaggerated neuroinflammatory responses in the outer retina of APPswe/PS1 bigenic mice following cyclic intensive light exposure (CILE), whereas controls remained little change contrasted with age-matched non-transgenic littermates. CILE-induced degenerative changes in RPE are further confirmed by transmission electron microcopy and manifest as formation of basal laminar deposits, irregular thickening of Bruch's membrane (BrM), deposition of outer collagenous layer (OCL) in the subretinal space, and vacuolation in the RPE. Immunofluorescence microscopy reveals drusenoid Aβ deposits in RPE as well as neovessels attached which are associated with disruption of RPE integrity and provoked neuroinflammatory response as indicated by markedly increased retinal infiltration of microglia. Moreover, both immunohistochemistry and Western blots detect an induction of vascular endothelial growth factor (VEGF) in RPE, which corroborates increased CNV in the outer retina in the bigenic mice challenged by CILE.
Conclusions
Our findings demonstrate that degenerative changes in the outer retina in the APPswe/PS1 bigenic mouse induced by CILE are consistent with these in AMD. These results suggest that an Alzheimer's transgenic animal model with accumulation of Aβ deposits might be an alternative animal model for AMD, if combined with other confounding factors such as intensive light exposure for AMD.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,General Neuroscience
Reference54 articles.
1. de Jong PT: Age-related macular degeneration. N Engl J Med. 2006, 355 (14): 1474-1485. 10.1056/NEJMra062326.
2. Hageman GS, Gehrs K, Johnson LV, Anderson D: Age-Related Macular Degeneration (AMD). Edited by: Kolb H, Fernandez E, Nelson R. 2008, Webvision: The Oragnization of the Retina and Visual System, Salt Lake City (UT): University of Utah Health Sciences Center, 1995, [http://www.ncbi.nlm.nih.gov/books/NBK27323/]
3. Kaarniranta K, Salminen A, Haapasalo A, Soininen H, Hiltunen M: Age-Related Macular Degeneration (AMD): Alzheimer's Disease in the Eye?. J Alzheimers Dis. 2011, 24 (4): 615-631.
4. Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J: Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest. 2006, 116 (2): 378-385. 10.1172/JCI25843.
5. Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL: Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis. 2003, 9: 184-190.
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献