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D. M. Wu, D. G. Puro; Hyperoxia Modulates the Physiology of the Developing Retinal Microvasculature. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4459.
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© ARVO (1962-2015); The Authors (2016-present)
In retinopathy of prematurity (ROP), fluctuating oxygen levels may reversibly alter blood flow prior to the onset of permanent structural changes. To test the hypothesis that ion channels play a role in the response of the developing retinal microvasculature to hyperoxia, we performed the first patch-clamp study of developing retinal microvessels.
A tissue print method was used to isolate retinal microvascular complexes from postnatal (P2-P6) rats. In freshly isolated microvessels, ionic conductances were monitored via perforated-patch pipette sealed onto a microvascular cell; simultaneous time-lapse photography allowed us to correlate changes in electrophysiological activity with vascular tone. An oxygen-enriched environment was created by bubbling a mixture of 95% O2/ 5% CO2 into the perfusate.
We found that hyperoxia caused the membrane potential of cells in postnatal retinal microvessels to increase by 7.8 ± 2.2 mV, p<0.005. This hyperoxia-induced hyperpolarization was due to the inhibition of a conductance whose reversal potential was near 0 mV. Hyperoxia also reversibly inhibited spontaneously occurring depolarizations, which were often observed in the postnatal microvasculature. Associated with these responses, microvascular relaxation and lumen dilation were detected in many of the monitored complexes. Because hyperpolarizing ion channels in adult retinal microvessels are redox-sensitive, we assessed the possibility that oxidants mediated the electrophysiological responses to hyperoxia. While we found that the oxidant, H2O2 (10-20 µM), also induced hyperpolarization in the immature retinal microvasculature, this voltage increase was larger (45 mV ± 2.9 in H2O2, p <0.001) than that induced by hyperoxia and was due to the activation of a current whose reversal potential was near EK, (i.e., -103 mV) and with a sensitivity to the KATP channel blocker glibenclamide. Thus H2O2 did not mimic the microvascular response to hyperoxia.
In the microvasculature of the postnatal rat, hyperoxia causes membrane potentials to increase, spontaneous depolarizations to cease, microvascular cells to relax, and vessel lumens to dilate. The hyperoxia-induced hyperpolarization is due to the inhibition of a non-specific cation conductance by an oxidant-independent mechanism. Our demonstration that ion channels play a role in the response of the immature retinal microvasculature to hyperoxia supports the idea that modification of ion channel activity is a possible strategy for altering events early in the course of ROP.
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