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R. Ray, D. Yoon, M. M. Abd-El-Barr, J. T. Prchal, S. M. Wu, E. Holz, T. A. Albini, P. E. Carvounis; Electroretinographic Findings in Knockin Mice With Gain of Function and Loss of Function Erythropoietin Receptor Signaling. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4943.
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© ARVO (1962-2015); The Authors (2016-present)
A growing body of evidence suggests that erythropoietin (Epo) plays a role in angiogenesis and neuroprotection. To investigate the possible role of erythropoietin in the retina we performed electroretinography in transgenic mice with gain-of-function and loss-of-function erythropoietin receptors (EpoR).
The animal models of increased and decreased Epo signaling were previously generated by homologous recombination in mouse embryonic stem cells. The murine EpoR gene was replaced with a gain-of-function mutant human EPOR (mthEPOR, from a patient with primary familial polycythemia) and with a loss-of-function wild-type human EPOR gene (wthEPOR) (PNAS, 98:986, 2001). 3 mthEPOR and 4 wthEPOR homozygotes underwent simultaneous bilateral dark-adapted electroretinography at 4 and 12 months of age.
At 4 months mthEPOR mice had a greater saturated a-wave amplitude compared to wthEPOR mice (510±31µV (mean±SEM) compared to 410±26µV, p=0.034), while the difference in maximum b-wave amplitude did not reach statistical significance (mthEPOR mice 490±38µV compared to wthEPOR 437±37µV). At 12 months mthEPOR mice had a statistically greater maximum b-wave amplitude compared to wthEPOR (400±8µV compared to 232±17µV, p=0.0006) mice while the difference in saturated a-wave amplitude failed to reach statistical significance (452±27µV compared to 367±21µV, p=0.21).
The greater a- and b- wave amplitudes found in the gain-of-function EpoR signaling mice may indicate that erythropoietin is a neurotrophic factor in the neurosensory retina. Histological analyses may corroborate structural differences that account for our electroretinographic findings.
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