May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
A Crystallin Protects Photoreceptors From Mitochondrial Oxidative Stress in Experimental Autoimmune Uveitis
Author Affiliations & Notes
  • S. Saraswathy
    Pathology, Doheny Eye Institute, Los Angeles, California
  • S. P. Bhat
    Geffen School of Medicine at UCLA, Los Angeles, California
  • E. F. Wawrousek
    Transgenic Animal and Genome Manipulation Section, NIH, Bethesda, Maryland
  • N. A. Rao
    Pathology, Doheny Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships S. Saraswathy, None; S.P. Bhat, None; E.F. Wawrousek, None; N.A. Rao, None.
  • Footnotes
    Support NIH Grant EY015714, NIH Grant EY03040
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1351. doi:https://doi.org/
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      S. Saraswathy, S. P. Bhat, E. F. Wawrousek, N. A. Rao; A Crystallin Protects Photoreceptors From Mitochondrial Oxidative Stress in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1351. doi: https://doi.org/.

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

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Abstract

Purpose:: We previously demonstrated marked upregulation of αA-crystallin in the photoreceptors in response to mitochondrial oxidative stress in early experimental autoimmune uveitis (EAU). In vitro this protein inhibited activation of proapoptotic factors. For the present study, we used αA-crystallin knockout mice to test the hypothesis that αA-crystallin may protect photoreceptors from apoptotic cell death during early EAU.

Methods:: EAU was induced in 129Sv (wild type) and αA-/- mice by injecting bovine interphotoreceptor retinoid-binding protein (IRBP). Other nonimmunized 129SV mice were used as additional controls. Ten eyes from each group were examined for inflammatory cell infiltration using hematoxylin-eosin staining on different postimmunization (PI.) days. Apoptotic changes in the retina were followed using TUNEL staining. RNA transcript level of 84 genes related to apoptosis and its signaling pathway in the EAU and control retinas were estimated by quantitative PCR.

Results:: The experimental 129SV (wild type) mice developed typical histologic features seen in of EAU with infiltration of macrophages in the retina and uvea on PI. day 17. On PI day 14 none of these animals showed EAU associated changes and apoptosis of the photoreceptors was not detected. In contrast, on PI. day 14, in the αA-/- mice there was macrophage infiltration in the retina and uvea with the photoreceptor damage, associated with significantly higher number of TUNEL-positive cells.

Conclusions:: The data obtained thus far with investigations on the αA-/- mice suggest that during early EAU (PI day 14) the induced elevated expression of αA crystallin (absent in the αA-/- mice) is associated with the protection of the photoreceptors from apoptotic cell death resulting from mitochondrial oxidative stress in the wild type mice.

Keywords: uveitis-clinical/animal model • crystallins • photoreceptors 
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