March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Endothelin Receptor A Antagonist Enhances Light-induced Damage In The Mouse Retina
Author Affiliations & Notes
  • Vicente Bermudez
    Cell and Molecular Medicine, Universidad Austral - FCB, Pilar, Argentina
  • Marisa A. Cubilla
    Cell and Molecular Medicine, Universidad Austral - FCB, Pilar, Argentina
  • Tomas P. Bachor
    Cell and Molecular Medicine, Universidad Austral - FCB, Pilar, Argentina
  • Maximiliano Olivera
    Cell and Molecular Medicine, Universidad Austral - FCB, Pilar, Argentina
  • Angela M. Suburo
    Cell and Molecular Medicine, Universidad Austral - FCB, Pilar, Argentina
  • Footnotes
    Commercial Relationships  Vicente Bermudez, None; Marisa A. Cubilla, None; Tomas P. Bachor, None; Maximiliano Olivera, None; Angela M. Suburo, None
  • Footnotes
    Support  PICTO Austral 2008-0090
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2571. doi:
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      Vicente Bermudez, Marisa A. Cubilla, Tomas P. Bachor, Maximiliano Olivera, Angela M. Suburo; Endothelin Receptor A Antagonist Enhances Light-induced Damage In The Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2571.

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

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Abstract

Purpose: : Exposure to excessive white light induces retinal degeneration or exacerbates the rate of photoreceptor apoptosis in several retinal diseases. In previous studies we demonstrated that stimulation of the endothelinergic pathways could intervene in photoreceptor death control. In this work we analyzed whether the endothelinergic antagonists Tezosentan (ETRA and ETRB) and Clazosentan (ETRA) could modify the course of light-induced degeneration.

Methods: : Experimental work was done according to the ARVO Statement for the use of animals. Male Balb-c mice (5-7 weeks old), bred under standard illumination conditions (12:12 h light: dark; < 60 lux), remained in complete darkness for 24 h. Mice were separated in groups with standard illumination (< 60 lux) and groups exposed to intense light (1500 lux) for 4 days (n = 3 per group). During the exposure period, animals received saline solution, Tezosentan (10 mg/kg/day) or Clazosentan (10 mg/kg/day). Afterwards they were allowed to recover, without treatment under standard illumination for another 6 days. Mice were then anesthetized and their eyes enucleated. Seriate retina cryosections were stained with neutral red, and thickness of outer nuclear layer (ONL) was measured to determine the level of light-induced damage.

Results: : Damage to the retina was higher in the temporal than in the nasal retina, and the largest attrition retina occurred around the optic nerve head. In Tezosentan-treated mice, damage was not significantly different from that in control animals. By contrast, the retina of mice receiving Clazosentan during light exposure was more severely damaged than those receiving saline or Tezosentan.

Conclusions: : Our present findings indicate that inhibition of ETRA signaling increased vulnerability of photoreceptors to light-induced damage. ETRA are found in photoreceptor terminals (Torbidoni et al., 2005) and the RPE (Narayan et al., 2003). Activation of these receptors, either by ET-1 or ET-2, would be involved in photoreceptor survival. Retinal damage observed after Tezosentan treatment was similar to that of controls, suggesting that blockade of both receptors cancelled the pro-apoptotic effect of ETRA inhibition.

Keywords: retina • photoreceptors • retinal degenerations: cell biology 
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