title: Systemic treatment with erythropoietin protects the neurovascular unit in a rat model of retinal neurodegeneration.
abstract: Rats expressing a transgenic polycystic kidney disease (PKD) gene develop photoreceptor degeneration and subsequent vasoregression, as well as activation of retinal microglia and macroglia. To target the whole neuroglialvascular unit, neuro- and vasoprotective Erythropoietin (EPO) was intraperitoneally injected into four-week old male heterozygous PKD rats three times a week at a dose of 256 IU/kg body weight. For comparison EPO-like peptide, lacking unwanted side effects of EPO treatment, was given five times a week at a dose of 10 µg/kg body weight. Matched EPO treated Sprague Dawley and water-injected PKD rats were held as controls. After four weeks of treatment the animals were sacrificed and analysis of the neurovascular morphology, glial cell activity and pAkt localization was performed. The number of endothelial cells and pericytes did not change after treatment with EPO or EPO-like peptide. There was a nonsignificant reduction of migrating pericytes by 23% and 49%, respectively. Formation of acellular capillaries was significantly reduced by 49% (p<0.001) or 40% (p<0.05). EPO-treatment protected against thinning of the central retina by 10% (p<0.05), a composite of an increase of the outer nuclear layer by 12% (p<0.01) and in the outer segments of photoreceptors by 26% (p<0.001). Quantification of cell nuclei revealed no difference. Microglial activity, shown by gene expression of CD74, decreased by 67% (p<0.01) after EPO and 36% (n.s.) after EPO-like peptide treatment. In conclusion, EPO safeguards the neuroglialvascular unit in a model of retinal neurodegeneration and secondary vasoregression. This finding strengthens EPO in its protective capability for the whole neuroglialvascular unit.
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Busch
authors.affiliation: Sanofi Diabetes Research and Translational Medicine, Frankfurt, Germany.
authors.forename: Aimo
authors.initials: A
authors.lastname: Kannt
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kolibabka
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlotterer
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Jihong
authors.initials: J
authors.lastname: Lin
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000737:chemistry*; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry; D012162:Retinal Degeneration / Q000188:drug therapy*
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa