July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The Differential Effects of Amyloid-Beta Species on Retinal Physiology in the Rat - Potential Implications for Retinal Disease and Age-Related Macular Degeneration
Author Affiliations & Notes
  • Shiri Zayit-Soudry
    Ophthalmology, Rambam Health Care Campus, Haifa, Israel
    Technion-Israel Institute of Technology, Haifa, Israel
  • Efrat Na'aman
    Ophthalmology, Rambam Health Care Campus, Haifa, Israel
  • Sarah Ya'ari
    Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
  • Michael Mimouni
    Ophthalmology, Rambam Health Care Campus, Haifa, Israel
    Technion-Israel Institute of Technology, Haifa, Israel
  • Shadi Safuri
    Ophthalmology, Rambam Health Care Campus, Haifa, Israel
    Technion-Israel Institute of Technology, Haifa, Israel
  • Lior Liba
    Ophthalmology, Rambam Health Care Campus, Haifa, Israel
    Technion-Israel Institute of Technology, Haifa, Israel
  • Lihi Adler-Abramovich
    Oral Biology, Tel Aviv University, Tel Aviv, Israel
  • Ehud Gazit
    Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
  • Footnotes
    Commercial Relationships   Shiri Zayit-Soudry, None; Efrat Na'aman, None; Sarah Ya'ari, None; Michael Mimouni, None; Shadi Safuri, None; Lior Liba, None; Lihi Adler-Abramovich, None; Ehud Gazit, None
  • Footnotes
    Support  Israel Science Foundation #2346/16 (Protected Research Time)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2996. doi:
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      Shiri Zayit-Soudry, Efrat Na'aman, Sarah Ya'ari, Michael Mimouni, Shadi Safuri, Lior Liba, Lihi Adler-Abramovich, Ehud Gazit; The Differential Effects of Amyloid-Beta Species on Retinal Physiology in the Rat - Potential Implications for Retinal Disease and Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2996.

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

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Abstract

Purpose : Amyloid-β (Aβ), a constituent of drusen, was implicated in the pathophysiology of age -related macular degeneration (AMD). Accumulating evidence supports an association between retinal Aβ deposition and compromise of the retinal integrity, yet the major pathogenic Aβ species in the retina and the mechanism of Aβ-mediated neurotoxicity remain unknown. We aimed to investigate the impact of different Aβ species on retinal function and structure in the rat.

Methods : Wild type rats were treated with intravitreal administration of distinct Aβ assemblies in the right eye, whereas the left eye was treated with the vehicle and served as control. Following the injection, retinal function and structure were studied longitudinally. Electroretinography, retinal histology and immunohistochemistry for Glial Fibrillary Acidic Protein (GFAP), a marker of retinal stress, were compared between treated and fellow eyes. Fluorescence labeling of Aβ species was used to follow their assembly to the retinal tissue, and immunostaining for Aβ characterized the nature of aggregates found in situ.

Results : Fibrillar (Aβ40, Aβ42) and oligomeric (Aβ42) preparations were synthesized. Assemblies possessed clear hallmarks of ordered amyloid structures based on transmission electron microscopy, spectroscopy and ThT Fluorescence. Electroretinography (ERG) in treated rats demonstrated a differential toxic effect of Aβ species. Oligomeric Aβ42 inflicted the strongest toxic effect, manifesting diminished ERG responses through 30 days post injection. A lesser retinal cytotoxic effect was noted following injection of fibrillar Aβ42, whereas no retinal compromise was recorded in response to Aβ40 fibrils. The toxic effect of Aβ42 organizations was further reflected by retinal glial response in treated eyes, evident by positive GFAP labeling and by internalization of the Aβ assemblies into Müller cells.

Conclusions : Our results provide conceptual evidence of the retinal toxicity of Aβ in vivo, and promote the mechanistic understanding of the pathogenicity of particular Aβ species. Stratifying the impact of pathological Aβ aggregation in the retina may enhance the understanding of amyloid-mediated retinal neurodegeneration, and may merit further investigation as a therapeutic avenue in AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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