Cataract Aggravates Alzheimer-Like Pathologies and Cognitive Deficits in an APP/PS1 Mouse Model
Zhao Geng1,2,4,6 · Zhong‑Yuan Yu2,4 · Jun Tan6 · Xuan‑Yue Wang3 · Gui‑Hua Zeng2,4 · Jiang‑Hui Li2,4 · Yu‑Di Bai2,4 · Xiao‑Qin Zeng2,4 · Yu‑Peng Zhu2,4 · Cheng‑Rong Tan2,4 · An‑Yu Shi2,4 · Yu‑Hui Liu2,4 · Xian‑Le Bu2,4 · Zi Ye1 · Yan‑Jiang Wang2,3,4,5 · Zhao‑Hui Li11 Senior Department of Ophthalmology, The Third Medical Centre of PLA General Hospital, Beijing 100853, China
2 Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing 400042, China
3 Institute of Brain and Intelligence, Third Military Medical University, Chongqing 400038, China
4 Chongqing Key Laboratory of Aging and Brain Diseases, Chongqing 400042, China
5 Department of Neurology, The First Afliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
6 Department of Ophthalmology, Daping Hospital, Third Military Medical University, Chongqing 400042, China
Abstract
Clinical investigations have suggested a potential link between cataracts and Alzheimer’s disease (AD). However, whether cataract has an impact on the progression of AD remains unclear. The objective of this research was to determine the relationship between cataracts and AD. A cataract model was established in APP/PS1 [mutant amyloid precursor protein (APP) and a mutant presenilin-1 (PS1) gene] mice via lens puncture. Behavioural assays were used to evaluate cognitive function. Immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assays (ELISA) were applied to detect AD-related pathology. Visual signals were markedly obstructed following surgery to induce cataracts, and these mice presented an increased cerebral amyloid-beta (Aβ) load, while no significant alterations in the levels of enzymes associated with Aβ metabolism were detected. In addition, compared with control mice, cataract model mice presented increased astrogliosis and microgliosis, along with elevated levels of proinflammatory factors. Moreover, cataract model mice presented more pronounced cognitive impairments than did control mice. Our study offers experimental confirmation that cataract considerably contributes to the pathogenesis of AD, thereby emphasizing the importance of visual signals in maintaining cognitive well-being.
Keywords
Cataract; Alzheimer’s disease; Aβ burden; Visual impairment; Behavioural defcits
