{"doi":"10.1523/jneurosci.1288-04.2004","title":"Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration","abstract":"<jats:p>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.</jats:p>","journal":"The Journal of Neuroscience","year":2004,"id":650674,"datarank":0.7181237614173069,"base_score":4.787491742782046,"endowment":4.787491742782046,"self_citation_contribution":0.7181237614173069,"citation_network_contribution":0.0,"self_endowment_contribution":0.7181237614173069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":119,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1696643,"name":"Andreas Wenzel","orcid":null,"position":1,"is_corresponding":false},{"id":1696644,"name":"Dinu Stanescu","orcid":null,"position":2,"is_corresponding":false},{"id":399082,"name":"Marijana Samardzija","orcid":"0000-0003-0991-4653","position":3,"is_corresponding":false},{"id":1696646,"name":"Svenja Hotop","orcid":null,"position":4,"is_corresponding":false},{"id":1696648,"name":"Mathias Groszer","orcid":null,"position":5,"is_corresponding":false},{"id":1696649,"name":"Muna Naash","orcid":null,"position":6,"is_corresponding":false},{"id":404968,"name":"Max Gassmann","orcid":"0000-0003-2750-8878","position":7,"is_corresponding":false},{"id":1696650,"name":"Charlotte Remé","orcid":null,"position":8,"is_corresponding":false},{"id":399083,"name":"Christian Grimm","orcid":"0000-0001-9318-4352","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration","abstract":"<jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":4.787491742782046,"endowment":4.787491742782046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15215287","pmcid":"PMC2929919","openalex_id":"https://openalex.org/W1999971491","authors":[],"funders":[{"funder_name":"NEI NIH HHS","grant_id":"EY12190","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R56 EY010609","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY010609","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P20 RR017703","title":null},{"funder_name":"NEI NIH HHS","grant_id":"EY-10609","title":null},{"funder_name":"NEI NIH HHS","grant_id":"P30 EY012190","title":null},{"funder_name":"National Institutes of Health","grant_id":"5P20RR017703-05","title":"COBRE:OUHSC: IMAGE ACQUISITION &PRODUCTION CORE"},{"funder_name":"National Institutes of Health","grant_id":"5R01EY010609-02","title":"MECHANISMS OF PHOTORECEPTOR CELLS DEGENERATION"}],"total_grants":8,"fwci":2.8383,"citation_percentile":0.90728466,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":5},{"year":2014,"count":3},{"year":2015,"count":8},{"year":2016,"count":3},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":2}],"oa_status":"bronze","license":"CC BY NC SA","oa_locations":[{"url":"https://www.jneurosci.org/content/jneuro/24/25/5651.full.pdf","host_type":"journal"},{"url":"https://www.jneurosci.org/content/jneuro/24/25/5651.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.1288-04.2004","host_type":"publisher"},{"url":"https://doi.org/10.1523/jneurosci.1288-04.2004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15215287","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2929919","host_type":"repository"},{"url":"http://www.jneurosci.org/content/24/25/5651.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.1523/jneurosci.1288-04.2004","host_type":""}],"fields_of_study":["Retinal Development and Disorders","Erythropoietin and Anemia Treatment","Retinal Diseases and Treatments","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Animals","Erythropoietin","Humans","Immunohistochemistry","Light","Mice, Transgenic","Mutation","Phosphoric Diester Hydrolases","Photoreceptor Cells","Recombinant Proteins","Retina","Retinal Degeneration","Rhodopsin","Apoptosis","Protein Subunits","Mice"],"keywords":["Retinal degeneration","Retinitis pigmentosa","Photoreceptor cell","Retina","Erythropoietin","Biology","Retinal","Genetically modified mouse","Transgene","Programmed cell death","Macular degeneration","Neuroprotection","Gene therapy of the human retina","Apoptosis","Cell biology","Neuroscience","Endocrinology","Medicine","Genetics","Ophthalmology","Biochemistry","Rhodopsin","Light","Phosphoric Diester Hydrolases","Mice, Transgenic","Immunohistochemistry","Recombinant Proteins","Mice","Protein Subunits","Mutation","Animals","Humans","Photoreceptor Cells"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T05:55:15.759663Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}