June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Peptide-based immunotherapy against oxidized elastin ameliorates pathology in mouse model of smoke-induced ocular injury
Author Affiliations & Notes
  • Baerbel Rohrer
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
    Research Services, VA Medical Center Ralph H Johnson, Charleston, South Carolina, United States
  • Nathaniel Parsons
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Balasubramaniam Annamalai
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Crystal Nicholson
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Elisabeth Obert
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • Bryan W. Jones
    Ophthalmology, University of Utah Health, Salt Lake City, Utah, United States
  • Andrew D Dick
    Ophthalmology, University of Bristol, Bristol, Bristol, United Kingdom
  • Footnotes
    Commercial Relationships   Baerbel Rohrer None; Nathaniel Parsons None; Balasubramaniam Annamalai None; Crystal Nicholson None; Elisabeth Obert None; Bryan Jones None; Andrew Dick Novartis, Affybody, UCB, Hubble Tx, Code C (Consultant/Contractor), Janssen Pharmaceuticals, Meira GTX, Code F (Financial Support)
  • Footnotes
    Support  Funding for this project was provided in part by the National In-stitutes of Health (NIH) R01EY019320 (BR), R01EY015128 (BWJ), R01EY028927 (BWJ) and P30EY014800 (BWJ), the Department of Veterans Affairs RX000444 and BX003050 (BR), the South Carolina SmartState Endowment (BR), and an Unrestricted Research Grant from Research to Prevent Blindness, New York, NY to the Department of Ophthalmology & Visual Sciences, University of Utah. ADD is supported in part through the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4600 – F0392. doi:
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    • Get Citation

      Baerbel Rohrer, Nathaniel Parsons, Balasubramaniam Annamalai, Crystal Nicholson, Elisabeth Obert, Bryan W. Jones, Andrew D Dick; Peptide-based immunotherapy against oxidized elastin ameliorates pathology in mouse model of smoke-induced ocular injury. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4600 – F0392.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of blindness in western populations. It is associated with an overactive complement system, and an increase in circulating antibodies against certain epitopes, including elastin has been reported. Aging and AMD is associated with a loss of the elastin layer of Bruch’s membrane (BrM; PMID: 15632016), which can be mimicked in the smoke-induced ocular pathology (SIOP) model in mouse. Of relevance, we previously showed that immunization with elastin peptide oxidatively modified by cigarette smoke (ox-elastin), exacerbated structural and functional damage in SIOP (PMID: 32207814 ). Here we asked whether ox-elastin peptide-based immunotherapy (PIT) ameliorates damage.

Methods : Mice were exposed to cigarette smoke for 6 months. C57BL/6J mice were injected with ox-elastin peptide at two doses via weekly subcutaneous administration, FcgR-/- and uninjected C57BL/6J mice served as controls. Retinal function was assessed by OKR, morphology by electron microscopy, and complement activation, antibody deposition and mechanisms of immunological tolerance were assessed by Western blotting and ELISA.

Results : Elimination of Fcg receptors, preventing antigen/antibody-dependent cytotoxicity, protected against SIOP. Mice receiving PIT with low dose ox-elastin (LD-PIT) exhibited reduced humoral immunity, reduced complement activation and IgG/IgM deposition in the RPE/choroid, and largely a preserved BrM and improved visual function. LD-PIT reduced IFNg and increased IL-4 within RPE/choroid. In contrast, the high dose PIT was not protective.

Conclusions : Our data further support ox-elastin role in ocular damage in SIOP in part via elastin-specific antibodies, and support the corollary that PIT with ox-elastin attenuates ocular pathology. Overall, damage is associated with complement activation, antibody-dependent cell-mediated cytotoxicity, and altered cytokine signature. Finally, peptide-based immunotherapy might be a suitable strategy for the prevention of AMD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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