title: Constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration.
abstract: Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced 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 light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (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, light-induced 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.
authors.affiliation: Laboratory for Retinal Cell Biology, University Eye Hospital, CH-8091 Zurich, Switzerland. cgrimm@opht.unizh.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Dinu
authors.initials: D
authors.lastname: Stanescu
authors.forename: Marijana
authors.initials: M
authors.lastname: Samardzija
authors.forename: Svenja
authors.initials: S
authors.lastname: Hotop
authors.forename: Mathias
authors.initials: M
authors.lastname: Groszer
authors.forename: Muna
authors.initials: M
authors.lastname: Naash
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Charlotte
authors.initials: C
authors.lastname: Remé
mesh_terms: D000818:Animals; D017209:Apoptosis; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008027:Light; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D010786:Photoreceptor Cells / Q000473:pathology / Q000528:radiation effects; D021122:Protein Subunits / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D012160:Retina / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D012243:Rhodopsin / Q000235:genetics
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D004921:Erythropoietin; D012243:Rhodopsin; D010727:Phosphoric Diester Hydrolases