Vulnerability of the retinal microvasculature to oxidative stress: ion channel-dependent mechanisms.

American Journal of Physiology. Cell Physiology
Masanori FukumotoDonald G Puro

Abstract

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. Using H(2)O(2) to cause oxidative stress in microvascular complexes freshly isolated from the adult rat retina, we assessed ionic currents, cell viability, intracellular oxidants, and cell calcium by using perforated-patch recordings, trypan blue dye exclusion, and fura-2 fluorescence, respectively. Supporting a role for the oxidant-sensitive ATP-sensitive K (K(ATP)) channels, we found that these channels are activated during exposure of retinal microvessels to H(2)O(2). Furthermore, their inhibition by glibenclamide significantly lessened H(2)O(2)-induced microvascular cell death. Additional experiments established that by increasing the influx of calcium into microvascular cells, the K(ATP) channel-mediated hyperpolarization boosted the vulnerability of these cells to oxidative stress. In addition to the K(ATP) channel-dependent mechanism for increasing the lethality of oxidative stress, we also found that the vulnerability of cells in the capilla...Continue Reading

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Citations

Nov 5, 2013·Trends in Endocrinology and Metabolism : TEM·Rafael SimóUNKNOWN European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR)
Aug 20, 2015·Biomolecules·Anton HermannThomas M Weiger
Jun 6, 2016·Experimental Eye Research·Andrey V DmitrievRobert A Linsenmeier
Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Donald G PuroDolly A Padovani-Claudio
Apr 19, 2018·American Journal of Physiology. Cell Physiology·Donald G Puro
Dec 1, 2018·Vestnik oftalmologii·S V SdobnikovaA L Sidamonidze
May 7, 2021·International Ophthalmology·Deepak SoniBrijesh Takkar

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