Jian Yang1,2, Jing Yang1,3, Yuyan Li2, Yungen Xu2, Chongzhao Ran4. 1. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. 2. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. 3. School of Pharmaceutical Science, Soochow University, Suzhou, 215006, China. 4. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA. cran@nmr.mgh.harvard.edu.
Abstract
PURPOSE: Near-infrared fluorescence (NIRF) imaging has been widely used in preclinical studies; however, its low tissue penetration represents a daunting problem for translational clinical imaging of neurodegenerative diseases. The retina is known as an extension of the central nerve system (CNS), and it is widely considered as a window to the brain. Therefore, the retina can be considered as an alternative organ for investigating neurodegenerative diseases, and an eye represents an ideal NIRF imaging organ, due to its minimal opacity. PROCEDURES: NIRF ocular imaging (NIRFOI), for the first time, was explored for imaging of Alzheimer's disease (AD) via utilizing "smart" fluorescent probes CRANAD-X (X = - 2, - 3, - 30, - 58, and - 102) for amyloid beta (Aβ), and CRANAD-61 for reactive oxygen species (ROS). Mice were intravenously injected the fluorescence dyes and images from the eyes were captured with an IVIS imaging system at different time points. RESULTS: All of the tested NIRF probes could be used to differentiate transgenic AD mice and WT mice, and NIRFOI could provide much higher sensitivity for imaging Aβs than NIRF brain imaging did. Our data suggested that NIRFOI could capture the imaging signals from both soluble and insoluble Aβ species. Moreover, we demonstrated that NIRFOI with CRANAD-102 could be used to monitor the therapeutic effects of BACE-1 inhibitor LY2811376. Compared to NIRF brain imaging, NIRFOI provided a larger change of Aβ levels before and after LY2811376 treatment. In addition, we demonstrated that CRANAD-61 could be used to image reactive oxygen species in the eyes. CONCLUSION: The large detection margin by NIRFOI is very important for both diagnosis and therapy response monitoring. Compared to fluorescence microscopic imaging, NIRFOI captures signals with a wide angle (large field of view (FOV)) and can be used to detect soluble Aβs. We believe that NIRFOI has remarkable translational potential for future human studies and can be a potential imaging technology for fast, cheap, accessible, and reliable screening of AD in the future.
PURPOSE: Near-infrared fluorescence (NIRF) imaging has been widely used in preclinical studies; however, its low tissue penetration represents a daunting problem for translational clinical imaging of neurodegenerative diseases. The retina is known as an extension of the central nerve system (CNS), and it is widely considered as a window to the brain. Therefore, the retina can be considered as an alternative organ for investigating neurodegenerative diseases, and an eye represents an ideal NIRF imaging organ, due to its minimal opacity. PROCEDURES: NIRF ocular imaging (NIRFOI), for the first time, was explored for imaging of Alzheimer's disease (AD) via utilizing "smart" fluorescent probes CRANAD-X (X = - 2, - 3, - 30, - 58, and - 102) for amyloid beta (Aβ), and CRANAD-61 for reactive oxygen species (ROS). Mice were intravenously injected the fluorescence dyes and images from the eyes were captured with an IVIS imaging system at different time points. RESULTS: All of the tested NIRF probes could be used to differentiate transgenicADmice and WT mice, and NIRFOI could provide much higher sensitivity for imaging Aβs than NIRF brain imaging did. Our data suggested that NIRFOI could capture the imaging signals from both soluble and insoluble Aβ species. Moreover, we demonstrated that NIRFOI with CRANAD-102 could be used to monitor the therapeutic effects of BACE-1 inhibitor LY2811376. Compared to NIRF brain imaging, NIRFOI provided a larger change of Aβ levels before and after LY2811376 treatment. In addition, we demonstrated that CRANAD-61 could be used to image reactive oxygen species in the eyes. CONCLUSION: The large detection margin by NIRFOI is very important for both diagnosis and therapy response monitoring. Compared to fluorescence microscopic imaging, NIRFOI captures signals with a wide angle (large field of view (FOV)) and can be used to detect soluble Aβs. We believe that NIRFOI has remarkable translational potential for future human studies and can be a potential imaging technology for fast, cheap, accessible, and reliable screening of AD in the future.
Authors: Yuchun Tsai; Bin Lu; Alexander V Ljubimov; Sergey Girman; Fred N Ross-Cisneros; Alfredo A Sadun; Clive N Svendsen; Robert M Cohen; Shaomei Wang Journal: Invest Ophthalmol Vis Sci Date: 2014-01-29 Impact factor: 4.799
Authors: Xueli Zhang; Yanli Tian; Can Zhang; Xiaoyu Tian; Alana W Ross; Robert D Moir; Hongbin Sun; Rudolph E Tanzi; Anna Moore; Chongzhao Ran Journal: Proc Natl Acad Sci U S A Date: 2015-07-21 Impact factor: 11.205
Authors: Yosef Koronyo; David Biggs; Ernesto Barron; David S Boyer; Joel A Pearlman; William J Au; Shawn J Kile; Austin Blanco; Dieu-Trang Fuchs; Adeel Ashfaq; Sally Frautschy; Gregory M Cole; Carol A Miller; David R Hinton; Steven R Verdooner; Keith L Black; Maya Koronyo-Hamaoui Journal: JCI Insight Date: 2017-08-17
Authors: Clifford R Jack; Michael Garwood; Thomas M Wengenack; Bret Borowski; Geoffrey L Curran; Joseph Lin; Gregor Adriany; Olli H J Gröhn; Roger Grimm; Joseph F Poduslo Journal: Magn Reson Med Date: 2004-12 Impact factor: 4.668
Authors: D R Borchelt; G Thinakaran; C B Eckman; M K Lee; F Davenport; T Ratovitsky; C M Prada; G Kim; S Seekins; D Yager; H H Slunt; R Wang; M Seeger; A I Levey; S E Gandy; N G Copeland; N A Jenkins; D L Price; S G Younkin; S S Sisodia Journal: Neuron Date: 1996-11 Impact factor: 17.173
Authors: Don H Anderson; Kevin C Talaga; Alexander J Rivest; Ernesto Barron; Gregory S Hageman; Lincoln V Johnson Journal: Exp Eye Res Date: 2004-02 Impact factor: 3.467
Authors: Michael Yamakawa; Samuel M Santosa; Neeraj Chawla; Evguenia Ivakhnitskaia; Matthew Del Pino; Sebastian Giakas; Arnold Nadel; Sneha Bontu; Arjun Tambe; Kai Guo; Kyu-Yeon Han; Maria Soledad Cortina; Charles Yu; Mark I Rosenblatt; Jin-Hong Chang; Dimitri T Azar Journal: Biochim Biophys Acta Gen Subj Date: 2020-03-12 Impact factor: 3.770