Identification of early-onset photoreceptor degeneration in transgenic mouse models of Alzheimer's disease
Jie Zhang,
Feng Gao,
Yuqian Ma,
Tian Xue,
Yong Shen
Affiliations
Jie Zhang
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China; Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China
Feng Gao
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China; Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China
Yuqian Ma
Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China; Eye Center at The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China
Tian Xue
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China; Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China; Eye Center at The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
Yong Shen
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230026, China; Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding author
Summary: Light sensitivity of the vertebrate retina relies on the integrity of photoreceptors, including rods and cones. Research in patients with Alzheimer's disease (AD) and in AD transgenic mice reports that accumulated amyloid-β (Aβ) plaques in the retina are toxic to retinal neurons. Moreover, Aβ plaques are deposited around the rods and cones, yet photoreceptor anomalies remain unclear in AD. Here, we identify the progressive degeneration of rods and cones characterized by impaired expression of phototransduction proteins, morphological alterations, functional deficits, and even cell loss. Furthermore, we demonstrate that cell senescence and necroptosis were involved in rod degeneration. Importantly, using in vivo scotopic electroretinogram, we detected rod degeneration in early-stage AD transgenic mice before Aβ plaques were observed in the brain. Moreover, we demonstrate that rod degeneration was among the earliest AD retinal manifestations compared with other types of retinal neurons. Overall, our study is the first to identify and detect in vivo, early-onset photoreceptor degeneration in AD.
