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C. Grimm, A. Wenzel, M. Samardzija, S. Hotop, M. Groszer, M. Naash, M. Gassmann, C.E. Remé; Constitutive overexpression of human erythropoietin in the mouse retina: Protection against induced but not against inherited retinal degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):830.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human erythropoietin protects the mouse retina against light–induced degeneration by inhibiting photoreceptor cell apoptosis. Using a transgenic mouse line that constitutively overexpresses human Epo (huEpo) mainly in neural tissues, we tested whether the presence of high levels of huEpo would also be beneficiary in mouse models of retinitis pigmentosa (RP). Methods: A transgenic mouse line (tg6) overexpressing human erythropoietin was crossed onto the rd1 and the VPP background using standard breeding schemes. Influence of the transgene on light–induced retinal degeneration was tested after exposure of tg6 to high levels of white light. The effect of tg6 on retinal degeneration in the rd1 and VPP mice was analyzed at different timepoints after birth using light microscopy and rhodopsin measurements. Levels of retinal Epo were determined by ELISA. Western blotting was used to demonstrate expression of various retinal proteins. Recombinant huEpo were applied intraperitoneally in VPP mice at post natal days 13, 15, 17 and 19. Results: The transgene in tg6 caused constitutively high levels of huEpo in the retina and protected against light–induced retinal degeneration. However, the presence of increased levels of huEpo did not affect course and extent of retinal degeneration in a light–independent (rd1) and a light–dependent (VPP) mouse model of RP. Repetitive intraperitoneal injections of huEpo into VPP mice did increase hematocrit values but did not influence onset and progression of the degeneration in the retina. Conclusions: Constitutively high levels of huEpo protect against light–induced photoreceptor apoptosis but cannot prevent inherited retinal degeneration in two mouse models of human RP. Repetitive application of huEpo did also not alter the course of the degeneration in the VPP mice. This suggests that inherited retinal degenerations may use alternative signaling pathways not influenced by Epo and argues against possible adaptive alterations in the retina that might have been induced by constitutively high levels of Epo in the tg6 animals.
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