March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Vulnerability Of The Retinal Microvasculature To Oxidative Stress: Ion Channel-dependent Mechanisms
Author Affiliations & Notes
  • Atsuko Nakaizumi
    Ophthalmology & Visual Sciences,
    University of Michigan, Ann Arbor, Michigan
  • Masanori Fukumoto
    Ophthalmology & Visual Sciences,
    University of Michigan, Ann Arbor, Michigan
  • Donald G. Puro
    Ophthalmology & Visual Sciences,
    Molecular & Integrative Physiology,
    University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  Atsuko Nakaizumi, None; Masanori Fukumoto, None; Donald G. Puro, None
  • Footnotes
    Support  EY12505, EY07003 and DK20572
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5776. doi:
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      Atsuko Nakaizumi, Masanori Fukumoto, Donald G. Puro; Vulnerability Of The Retinal Microvasculature To Oxidative Stress: Ion Channel-dependent Mechanisms. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5776.

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

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Purpose: : Although oxidative stress is a hallmark of important vascular disorders such as diabetic retinopathy, it remains unclear why the retinal microvasculature is particularly vulnerable to this pathophysiological condition. We postulated that redox-sensitive ion channels may play a role.

Methods: : Using H2O2 to cause oxidative stress in microvascular complexes freshly isolated from the adult rat retina, we assessed ionic currents, cell viability and cell calcium by using perforated-patch recordings, trypan blue dye exclusion and fura-2 fluorescence, respectively.

Results: : Supporting a role for the oxidant-sensitive KATP channels, we found that these channels are activated during exposure of retinal microvessels to H2O2. Furthermore, inhibition of KATP channels by glibenclamide significantly lessened H2O2-induced microvascular cell death. Additional experiments established that by increasing the influx of calcium into microvascular cells, the hyperpolarization caused by the H2O2-induced opening of KATP channels boosted the vulnerability of the retinal microvasculature to oxidative stress. In addition to this KATP channel-dependent mechanism for boosting the lethality of oxidative stress, we also found that the vulnerability of cells in the capillaries, but not in the arterioles, was further increased by a KATP channel-independent mechanism, which our experiments indicate is due to the oxidant-induced activation of calcium-permeable non-specific cation channels.

Conclusions: : Our findings support a working model in which both KATP channel-independent and KATP channel-dependent mechanisms render the capillaries of the retina particularly vulnerable to oxidative stress. Identification of these previously unappreciated mechanisms for boosting the lethality of oxidants provides new potential targets for pharmacologically limiting damage to the retinal microvasculature during periods of oxidative stress.

Keywords: retinal degenerations: cell biology • stress response • electrophysiology: non-clinical 

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