ARCAM-1 Facilitates Fluorescence Detection of Amyloid-Containing Deposits in the Retina
| Autor: | Jonathan H. Lin, Patricia M. Gaffney, John H. Kim, Heike Kroeger, Christina J. Sigurdson, Jerry Yang, Kevin J. Cao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Amyloid Biomedical Engineering Mice Transgenic Plaque Amyloid Article Retina law.invention Immunolabeling chemistry.chemical_compound Mice In vivo Confocal microscopy law Alzheimer Disease mental disorders medicine Animals Humans Amyloid beta-Peptides Chemistry amyloid imaging Retinal Alzheimer's disease Ophthalmology medicine.anatomical_structure Immunostaining |
| Zdroj: | Translational Vision Science & Technology |
| ISSN: | 2164-2591 |
| Popis: | Purpose To investigate the use of an amyloid-targeting fluorescent probe, ARCAM-1, to identify amyloid-containing deposits in the retina of a transgenic mouse model of Alzheimer's disease (AD) and in human postmortem AD patients. Methods Aged APP/PS1 transgenic AD and wild-type (WT) mice were given an intraperitoneal (IP) injection of ARCAM-1 and their retinas imaged in vivo using a fluorescence ophthalmoscope. Eyes were enucleated and dissected for ex vivo inspection of retinal amyloid deposits. Additionally, formalin-fixed eyes from human AD and control patients were dissected, and the retinas were stained using ARCAM-1 or with an anti-amyloid-β antibody. Confocal microscopy was used to image amyloid-containing deposits stained with ARCAM-1 or with immunostaining. Results Four out of eight APP/PS1 mice showed the presence of amyloid aggregates in the retina during antemortem imaging. Retinas from three human AD patients stained with ARCAM-1 showed an apparent increased density of fluorescently labeled amyloid-containing deposits compared to the retinas from two healthy, cognitively normal (CN) patients. Immunolabeling confirmed the presence of amyloid deposits in both the retinal neuronal layers and in retinal vasculature. Conclusions ARCAM-1 facilitates antemortem detection of amyloid aggregates in the retina of a mouse model for AD, and postmortem detection of amyloid-containing deposits in human retinal tissues from AD patients. These results support the hypothesis of AD pathology manifesting in the eye and highlight a novel area for fluorophore development for the optical detection of retinal amyloid in AD patients. Translational relevance This paper represents an initial examination for potential translation of an amyloid-targeting fluorescent probe to a retinal imaging agent for aiding in the diagnosis of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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