constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration elevation of erythropoietin epo concentrations by hypoxic preconditioning or application of recombinant human epo huepo protects the mouse retina against lightinduced degeneration by inhibiting photoreceptor cell apoptosis because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa rp we tested whether high levels of huepo would reduce apoptotic cell death in two mouse models of human rp we combined the two respective mutant mouse lines with a transgenic line tg6 that constitutively overexpresses huepo mainly in neural tissues transgenic expression of huepo caused constitutively high levels of epo in the retina and protected photoreceptors against lightinduced degeneration however the presence of high levels of huepo did not affect the course or the extent of retinal degeneration in a lightindependent rd1 and a lightaccelerated vpp mouse model of rp similarly repetitive intraperitoneal injections of recombinant huepo did not protect the retina in the rd1 and the vpp mouse lack of neuroprotection by epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of epo receptor our results suggest that apoptotic mechanisms during acute lightinduced photoreceptor cell death differ from those in genetically based retinal degeneration therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments