Jing Guo1 • Shaozhou Ni3 • Qihang Li4 • Jian-Zhi Wang1,2,* • Ying Yang1,*
1Department of Pathophysiology, School of Basic Medicine and Collaborative Innovation Center for Brain Science, Key Laboratory for Neurological Disorders of the Ministry of Education of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
3Emergency Department, Zhongnan Hospital of Wuhan University, Wuhan, China
4School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, China
Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer’s disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.