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Donald G Puro, Ryohsuke Kohmoto; Retinovascular physiology in the rat ROP model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5395.
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© ARVO (1962-2015); The Authors (2016-present)
Our objective was to employ a new experimental strategy to better understand the pathophysiology of ROP. Namely, we used the patch-clamp technique to monitor membrane potentials and to assess current-voltage relations in pre-retinal neovascular complexes and in the intra-retinal vasculature. Even though voltage is known to play a key role in vascular function, this study appears to be the first electrophysiological assessment of pathological neovessels.
Retinas with pre-retinal neovascularization were generated in Long-Evans rats by the 50/10 variable oxygen protocol devised by Penn and colleagues to create a model of ROP. In addition, we studied the retinal vasculatures of normal postnatal day (P)-5 and adult rats. In most experiments, voltages and currents were monitored via perforated-patch pipettes sealed onto pre- and intra-retinal vessels located in the intact ex vivo retina. Recordings were also obtained from vessels freshly isolated from ROP and normal retinas.
Perforated-patch recordings revealed that neovascular complexes located on the surface of the intact ex vivo ROP retina have the extraordinarily high resting membrane potential of -94 ± 6 mV (n=11; EK = -89 mV). The intra-retinal vasculature of ROP rats also has a very high membrane potential, i.e., -93 ± 10 mV (n = 10). These potentials are markedly greater (P ≤ 0.0003) than the voltages of vessels located in the adult (-51 ± 9 mV, n=9) or P-5 (-72 ± 8 mV, n=7) retina. Preliminary experiments indicate that the hyperpolarizing current generated by Na+/K+ pump activity is particularly large in pre-retinal neovessels. In addition, recordings from vessels isolated from ROP retinas indicate that independent of the intra-retinal vasculature, neovascular complexes generate high voltages.
This first patch-clamp study of ROP indicates that pathological neovascular complexes generate a large voltage that is transmitted to vessels located within the retina. A scenario to explore is that the extreme hyperpolarization driven by pre-retinal neovessels exerts a function-altering effect on the intra-retinal vasculature and thereby, contributes to the pathophysiology of ROP.
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