June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Aerosol Delivery of Thioflavin S Reveals Ab in the Retina of the 5XFAD Model of Alzheimer’s Disease
Author Affiliations & Notes
  • Sieun Lee
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
    Simon Fraser University, Coquitlam, British Columbia, Canada
  • Shawn Barton
    Radiology & Radiological Sciences, Vanderbilt University Medical Center, Tennessee, United States
  • Eleanor To
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Shaila Gunn
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Ahmad Sidiqi
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Jing Z Cui
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Hua Ren
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Mirza Faisal Beg
    Simon Fraser University, Coquitlam, British Columbia, Canada
  • Wellington Pham
    Radiology & Radiological Sciences, Vanderbilt University Medical Center, Tennessee, United States
  • Joanne A Matsubara
    Department of Ophthalmology & Visual Sciences, University of British Columbia, British Columbia, Canada
  • Footnotes
    Commercial Relationships   Sieun Lee, None; Shawn Barton, None; Eleanor To, None; Shaila Gunn, None; Ahmad Sidiqi, None; Jing Cui, None; Hua Ren, None; Mirza Beg, None; Wellington Pham, None; Joanne Matsubara, None
  • Footnotes
    Support  NIH R01AG061138-01A1
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 185. doi:
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      Sieun Lee, Shawn Barton, Eleanor To, Shaila Gunn, Ahmad Sidiqi, Jing Z Cui, Hua Ren, Mirza Faisal Beg, Wellington Pham, Joanne A Matsubara; Aerosol Delivery of Thioflavin S Reveals Ab in the Retina of the 5XFAD Model of Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2020;61(7):185.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The hallmark pathologic features of Alzheimer’s disease (AD) are amyloid beta (Ab) plaques and neurofibrillary tangles found in postmortem brain specimens or with invasive brain imaging in patients with advanced disease. A non-invasive and inexpensive screening method is needed for early detection and treatment of asymptomatic AD patients to improve therapeutic efficacy. The similarities between the brain and retina make the retina a suitable surrogate tissue to assess Ab load in AD. Using a novel aerosol delivery method, Thioflavin S (ThioS), a fluroprobe with high affinity to Ab, was administered to 5XFAD transgenic mouse models of AD to reveal ThioS bound to Ab in the retina.

Methods : 5XFAD (Tg, N=10) and age-matched wildtype (WT, N=18) underwent ThioS (2% w/v in ddH2O) nebulization for a period of 3 hours, repeated for two consecutive days. Animals were transcardially perfused 2 hours after the final nebulization. Eyes and brains were then dissected and processed for paraffin or frozen sectioning. Tissues were coverslipped for confocal microscopy using a Zeiss LSM 800/880. All tissues were scanned at identical settings, using 488nm and 543 nm (ThioS) and 405nm (DAPI, nuclei) wavelengths. Intensity of fluorescence was measure by custom software and normalized to negative control sections, and treated and untreated Tg and WT groups were compared.

Results : Paraffin cross sections and wholemounts revealed ThioS labeling in the nerve fiber (NFL) and ganglion cell layer (GCL) of the nebulized Tg retina, with ganglion cell profiles evident. Nebulized WT retina displayed sporadic labeling in the inner and outer plexiform layers (IPL, OPL). Alternate serial cross sections revealed 6E10 immunolabeling in NFL and GCL of Tg retina. Paired brain and eye tissues comparisons identified consistent Ab and ThioS labeling suggesting ThioS is a robust marker of Ab in the brain and eye of the Tg mouse.

Conclusions : Orally administered fluroprobes such as curcumin derivatives have been used for in vivo visualization of retinal Ab in humans, but suffers from low solubility and poor absorption in the gut. Using aerosol delivery systems may allow an improved method to deliver fluroprobes to bind retinal Ab. Our next step will be in vivo fSLO live imaging of fluroprobe-bound Ab in 5XFAD mice for a non-invasive method of detecting Ab, and potentially a novel method of predicting and diagnosing early AD.

This is a 2020 ARVO Annual Meeting abstract.

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