May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Systemic but Not Intravitreal Steroids Inhibit AP-1 in Light Exposed T4R Rhodopsin Mutant Dog Retina, but Neither Prevent Photoreceptor Degeneration
Author Affiliations & Notes
  • G. D. Aguirre
    Clinical Studies, Univ of Penn Sch Veterinary Med, Philadelphia, Pennsylvania
  • D. Gu
    Clinical Studies, Univ of Penn Sch Veterinary Med, Philadelphia, Pennsylvania
  • S. Pearce-Kelling
    Baker Institute, Cornell University, Ithaca, New York
  • Z. Li
    Clinical Studies, Univ of Penn Sch Veterinary Med, Philadelphia, Pennsylvania
  • G. M. Acland
    Baker Institute, Cornell University, Ithaca, New York
  • W. A. Beltran
    Clinical Studies, Univ of Penn Sch Veterinary Med, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  G.D. Aguirre, None; D. Gu, None; S. Pearce-Kelling, None; Z. Li, None; G.M. Acland, None; W.A. Beltran, None.
  • Footnotes
    Support  EY-06855, 13132, 001583, FFB, The ONCE Intern'l Prize, Van Sloun Fund, U of P Research Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4412. doi:https://doi.org/
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      G. D. Aguirre, D. Gu, S. Pearce-Kelling, Z. Li, G. M. Acland, W. A. Beltran; Systemic but Not Intravitreal Steroids Inhibit AP-1 in Light Exposed T4R Rhodopsin Mutant Dog Retina, but Neither Prevent Photoreceptor Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4412. doi: https://doi.org/.

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

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Abstract

Purpose: : AP-1 has been proposed as the key intermediate linking light exposure and photoreceptor cell death in rodent light damage models as steroid administration, which prevents light damage, is associated with AP-1 inhibition. Unlike the case in normal rodents, we have suggested that AP-1 is a cell survival rather than a cell death signal in the T4R RHO mutant dog retina (Gu et al., 2007). We now examine the role of steroids in inhibiting AP-1 activation and/or in preventing photoreceptor degeneration.

Methods: : T4R RHO mutant dogs were dark adapted overnight. Both eyes were dilated with mydriatics; the fundus of the left eye was photographed (~15-17 overlapping frames) using a Kowa RC-2 fundus camera, while the right eye was patched and unexposed to light. Dogs remained in the dark for 1-3 hrs after exposure for biochemical studies. 24 hrs prior to light exposure, some dogs were treated with systemic dexamethasone (DEX) or intravitreal/subconjunctival triamcinolone (TRIAM). AP-1 DNA binding activity was determined by EMSA, and phosphorylation of c-Fos and activation of ERK1/2 by immunoblotting; eyes were collected at 2 and 4 weeks after light exposure for histopathology.

Results: : Inhibition of AP-1 activation, and ERK1/2 and of c-Fos phosphorylation were found following systemic DEX treatment in light exposed T4R RHO mutant dog retinas. In contrast, AP-1 activation, phosphorylation of c-Fos and activation of ERK1/2 were not inhibited following light exposure in TRIAM-treated mutant retinas. In either case, however, extensive photoreceptor degeneration was found after light exposure.

Conclusions: : Intraocular or systemic steroids fail to prevent light induced photoreceptor degeneration in the T4R RHO mutant dog retina. Finding that systemic DEX prevents AP-1 activation, yet has no effect in preventing retinal light damage, further supports the hypothesis that, at least in the RHO mutant canine retina, AP-1 is not the cell-death signal.

Keywords: photoreceptors • retinal degenerations: hereditary • apoptosis/cell death 
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