Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Dry age-related macular degeneration like pathology in aged 5XFAD mice: Ultrastructure and microarray analysis

Sung Wook Park, Sora Im, Hyoung Oh Jun, Kihwang Lee, Young-Jun Park, Jin Hyoung Kim, Woo Jin Park, Young-Hoon Lee and Jeong Hun Kim _

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Oncotarget. 2017; 8:40006-40018. https://doi.org/10.18632/oncotarget.16967

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Abstract

Sung Wook Park1, 2, Sora Im3, Hyoung Oh Jun2, Kihwang Lee4, Young-Jun Park5, Jin Hyoung Kim2, Woo Jin Park3, Young-Hoon Lee6 and Jeong Hun Kim1,2,7

1 Department of Biomedical Sciences, Seoul National University College of Medicine, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea

2 Fight Against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea

3 Department of Life Sciences, Life Sciences Concentration Gwangju Institute of Science and Technology Cheomdan-Gwagiro, Buk-Gu, Gwangju, Republic of Korea

4 Department of Ophthalmology, Ajou University School of Medicine, World Cup-Ro, Yeongtong-Gu, Suwon-Si, Gyeonggi-Do, Republic of Korea

5 Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

6 Department of Oral Anatomy, School of Dentistry, Chonbuk National University, Deokjin-Gu, Jeonju-Si, Jeollabuk-Do, Republic of Korea

7 Institute of Oral Biosciences, Chonbuk National University, Deokjin-Gu, Jeonju-Si, Jeollabuk-Do, Republic of Korea

Correspondence to

Jeong Hun Kim, email:

Keywords: amyloid β, age-related macular degeneration, transmission electron microscopy, retinal pigment epithelium, microarray, Gerotarget

Received: September 02, 2016 Accepted: March 29, 2017 Published: April 08, 2017

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The two types of AMD are: dry and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD, there is no established mouse model that fully recapitulates the cardinal features of dry AMD. A lack of appropriate mouse model for dry AMD has hampered the translational research on the pathogenesis of the disease and the development of therapeutic agents. We hypothesized that 5XFAD mice, an animal model for the study of Alzheimer’s disease, can be used as a mouse model for dry AMD with regard to the amyloid beta (Aβ) related pathology. In this study, the ultrastructure of the retinal pigment epithelium (RPE) of 5XFAD mice was analyzed using transmission electron microscopy. Of importance, the aged 5XFAD mice show ultrastructural changes in the RPE and Bruch’s membrane (BM) that are compatible with the cardinal features of human dry AMD, including a loss of apical microvilli and basal infolding of the RPE, increased BM thickness, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laden phagosomes. In microarray-based analysis, the RPE complex of the aged 5XFAD mice shows differential gene expression profiles consistent with dry AMD in the inflammation response, immune reaction pathway, and decreased retinol metabolism. Taken together, we suggest that aged 5XFAD mice can be used as a mouse model of dry AMD to study Aβ related pathology and develop a new therapeutic approaches.


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