May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Auto-Immune Responses to Oxidatively Altered Self Proteins in the Retina Lead to the Development of Retinal Degeneration
Author Affiliations & Notes
  • V. L. Perez
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • X. Yang
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • M. E. Raybourn
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • R. Ufret
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • M. Yu
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • Y. Liang
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • R. Salomon
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • N. S. Peachey
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • J. G. Hollyfield
    Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
  • Footnotes
    Commercial Relationships V.L. Perez, None; X. Yang, None; M.E. Raybourn, None; R. Ufret, None; M. Yu, None; Y. Liang, None; R. Salomon, None; N.S. Peachey, None; J.G. Hollyfield, None.
  • Footnotes
    Support NIH KO8-EY014912 HIGHWIRE EXLINK_ID="48:5:1096:1" VALUE="EY014912" TYPEGUESS="GEN" /HIGHWIRE -03, EY015638 HIGHWIRE EXLINK_ID="48:5:1096:2" VALUE="EY015638" TYPEGUESS="GEN" /HIGHWIRE , EY014240 HIGHWIRE EXLINK_ID="48:5:1096:3" VALUE="EY014240" TYPEGUESS="GEN" /HIGHWIRE , GM21249, Research to Prevent Blindness, State of Ohio-BRTT 05-29 & The Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1096. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      V. L. Perez, X. Yang, M. E. Raybourn, R. Ufret, M. Yu, Y. Liang, R. Salomon, N. S. Peachey, J. G. Hollyfield; Auto-Immune Responses to Oxidatively Altered Self Proteins in the Retina Lead to the Development of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1096. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: Patients with age-related macular degeneration (AMD) have circulating auto-antibodies to carboxyethylpyrrole (CEP)-modified albumin. CEP albumin adducts are generated in the retinal photoreceptors in response to oxidative stress. The main goal of this work is to determine immunized mice with CEP-modified albumin leads to the generation of an immune response that induces AMD.

Methods:: C57BL/6 were immunized in the footpad with mouse serum albumin adducted with CEP (CEP-MSA) or non-adducted MSA emulsified in complete Freund adjuvant (CFA) followed with a subcutaneous challenge at day 10 with incomplete Freund adjuvant-CEP-MSA. Mice received a second subcutaneous challenge two months later with CFA-MSA. Fundus exams and electroretinograms (ERG) were performed at different time points. Anti-CEP antibodies in the serum were measured by ELISA. Animals were sacrificed at two months for histological examination of enucleated eyes. T cell priming to CEP-MSA was assessed in the lymph nodes and spleens using Interferon gamma (IFN-g), IL-4 and IL-2 ELISPOT assay in response to in vitro CEP-MSA stimulation. The role of adaptive immunity was tested in CFA-CEP-MSA immunized RAG KO mice deficient in T and B cells.

Results:: All C57BL/6 mice (7/7) that were immunized and challenged with CFA-CEP-MSA had increased titers of anti-CEP antibodies, in contrast to controls (0/7). Moreover, a significant number of CEP-MSA specific IFN-g and IL-2 producing T cells in lymph nodes and spleen of immunized mice and no IL-4 producing T cells were detected. Although clinical examination was unremarkable, histological analysis showed significant amount of photoreceptor loss and scattered vacuolization of the RPE in CEP-MSA C57BL/6 immunized mice only, similar to those described in early AMD. No ERG changes were noted. Immunized and challenged RAG KO mice had no pathological changes in the retina, correlating with the lack of T cell priming and the absence of anti-CEP auto-antibodies.

Conclusions:: Immune responses to a CEP adducted self-protein in the retina can lead to the generation of an adaptive immune response that results in retinal damage and possibly AMD. This demonstrates for the first time that an in vivo chemical modification induced by oxidative stress in a specific organ can lead to autoimmunity. Moreover, this represents a novel and unique animal model to study immune mechanisms that could lead to the development of AMD and could be used to develop new therapies.

Keywords: age-related macular degeneration • autoimmune disease • oxidation/oxidative or free radical damage 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×