{"doi":"10.1371/journal.pone.0226840","title":"Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo","abstract":"PURPOSE: To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore. METHODS: Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane-retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content. RESULTS: In darkness, baseline rod energy production and consumption are relatively high compared to that in light, and additional metabolic stimulation with DNP provoked thinning of the ELM-RPE region compared to saline injection in S6 mice; ELM-RPE thickness was unresponsive to DNP in B6 mice. Also, dark-adapted S6 mice given DNP showed a decrease in outer retina R1 values compared to saline injection in the inferior retina. In dark-adapted B6 mice, transretinal R1 values were unresponsive to DNP in superior and inferior regions. In light, with its relatively lower basal rod energy production and consumption, DNP caused ELM-RPE thinning in both S6 and B6 mice. CONCLUSIONS: The present results raise the possibility of non-invasively evaluating the mouse rod mitochondrial energy ecosystem using new DNP-assisted OCT and MRI in vivo assays.","journal":"PLoS ONE","year":2020,"id":77127,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":402009,"name":"Hailey Olds","orcid":"0000-0002-6408-8625","position":1,"is_corresponding":false},{"id":402010,"name":"Collin Richards","orcid":"0000-0002-9833-5938","position":2,"is_corresponding":false},{"id":403372,"name":"Joydip Joy","orcid":null,"position":3,"is_corresponding":false},{"id":403373,"name":"Tilman Rosales","orcid":null,"position":4,"is_corresponding":false},{"id":402011,"name":"Robert H. Podolsky","orcid":"0000-0003-3547-8859","position":5,"is_corresponding":false},{"id":402012,"name":"Karen Lins Childers","orcid":"0000-0002-7645-1583","position":6,"is_corresponding":false},{"id":332084,"name":"W. Brad Hubbard","orcid":"0000-0001-7018-0148","position":7,"is_corresponding":false},{"id":41890,"name":"Patrick G. Sullivan","orcid":"0000-0001-7418-4760","position":8,"is_corresponding":false},{"id":402013,"name":"Shasha Gao","orcid":"0000-0001-5751-7105","position":9,"is_corresponding":false},{"id":402014,"name":"Yichao Li","orcid":"0000-0003-2697-2556","position":10,"is_corresponding":false},{"id":402015,"name":"Haohua Qian","orcid":"0000-0002-1114-4697","position":11,"is_corresponding":false},{"id":402016,"name":"Robin Roberts","orcid":"0009-0001-1705-0747","position":12,"is_corresponding":false},{"id":402008,"name":"Bruce A. Berkowitz","orcid":"0000-0003-0291-2209","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T21:48:50.085103Z","pmid":"31923239","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":[]}