{"doi":"10.1111/j.1755-3768.2016.0179","title":"Nrf2‐ and PGC‐1<i>α</i>‐deficient mice: A novel animal model for disturbed proteostasis and RPE degeneration","abstract":"<jats:sec><jats:title>Summary</jats:title><jats:p>Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age‐related macular degeneration (AMD). Both of them participate in the regulation of proteostasis in the retina. Nrf2 and PGC‐1 transcription factors mediate cellular defence against oxidative stress. We describe a novel Nrf2 and PGC‐1 knock‐out mouse model that induces RPE degeneration. Aged Nrf2/PGC1 knock‐out mice developed RPE degeneration, associated with upregulation of lipid peroxidation marker 4‐HNE, ubiquitin protein aggregates, selective autophagy markers Beclin‐1, SQSTM1/p62 and LC3. These changes were accompanied by impaired visual function as assessed by ERG. Our findings suggest that combined Nrf2 and PGC‐1 deficiency increases oxidative stress and protein aggregation, and affects autophagy in RPE. Nrf2 and PGC‐1 knock‐out mouse model provides a novel tool to study role of proteostasis in the degeneration of RPE and autophagy as therapy target in the prevention of age‐related cellular damages.</jats:p></jats:sec>","journal":"Acta Ophthalmologica","year":2016,"id":674229,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"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":1761576,"name":"K. Kaarniranta","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nrf2‐ and PGC‐1<i>α</i>‐deficient mice: A novel animal model for disturbed proteostasis and RPE degeneration","abstract":"<jats:sec><jats:title>Summary</jats:title><jats:p>Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age‐related macular degeneration (AMD). Both of them participate in the regulation of proteostasis in the retina. Nrf2 and PGC‐1 transcription factors mediate cellular defence against oxidative stress. We describe a novel Nrf2 and PGC‐1 knock‐out mouse model that induces RPE degeneration. Aged Nrf2/PGC1 knock‐out mice developed RPE degeneration, associated with upregulation of lipid peroxidation marker 4‐HNE, ubiquitin protein aggregates, selective autophagy markers Beclin‐1, SQSTM1/p62 and LC3. These changes were accompanied by impaired visual function as assessed by ERG. Our findings suggest that combined Nrf2 and PGC‐1 deficiency increases oxidative stress and protein aggregation, and affects autophagy in RPE. Nrf2 and PGC‐1 knock‐out mouse model provides a novel tool to study role of proteostasis in the degeneration of RPE and autophagy as therapy target in the prevention of age‐related cellular damages.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W2519086149","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.11285623,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1755-3768.2016.0179","host_type":"publisher"},{"url":"http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1755-3768.2016.0179/fullpdf","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1755-3768.2016.0179","host_type":"journal"}],"fields_of_study":["Retinal Diseases and Treatments","Advanced Glycation End Products research","Genomics, phytochemicals, and oxidative stress"],"mesh_terms":[],"keywords":["Proteostasis","Autophagy","Retinal degeneration","Macular degeneration","Oxidative stress","Downregulation and upregulation","Cell biology","Biology","Retinal pigment epithelium","Degeneration (medical)","Retinal","Medicine","Endocrinology","Apoptosis","Pathology","Biochemistry","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T16:07:36.590945Z","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":[]}