{"doi":"10.18632/oncotarget.27380","title":"Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis <i>ex vivo</i> and <i>in vivo</i>","abstract":"// Stephanie L. Merrigan 1 , Bomina Park 2 , 3 , Zaheer Ali 4 , Lasse D. Jensen 4 , Timothy W. Corson 2 , 3 and Breand&#x00E1;n N. Kennedy 1 1 UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin D04 V1W8, Ireland 2 Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA 3 Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis,Indiana, USA 4 Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Link&#x00F6;ping University, Link&#x00F6;ping, Sweden Correspondence to: Breand&#x00E1;n N. Kennedy, email: brendan.kennedy@ucd.ie Keywords: developmental angiogenesis; pathological angiogenesis; ocular angiogenesis; calcitriol; 22-oxacalcitriol Received: July 22, 2019&emsp;&emsp;&emsp;&emsp; Accepted: October 19, 2019&emsp;&emsp;&emsp;&emsp; Published: February 04, 2020 ABSTRACT Aberrant ocular angiogenesis can underpin vision loss in leading causes of blindness, including neovascular age-related macular degeneration and proliferative diabetic retinopathy. Current pharmacological interventions require repeated invasive administrations, may lack efficacy and are associated with poor patient compliance and tachyphylaxis. Vitamin D has de novo anti-angiogenic properties. Here, our aim was to validate the ocular anti-angiogenic activity of biologically active vitamin D, calcitriol, and selected vitamin D analogue, 22-oxacalcitriol. Calcitriol induced a significant reduction in ex vivo mouse choroidal fragment sprouting. Viability studies in a human RPE cell line suggested non-calcemic vitamin D analogues including 22-oxacalcitriol have less off-target anti-proliferative activity compared to calcitriol and other analogues. Thereafter, the anti-angiogenic activity of 22-oxacalcitriol was demonstrated in an ex vivo mouse choroidal fragment sprouting assay. In zebrafish larvae, 22-oxacalcitriol was found to be anti-angiogenic, inducing a dose-dependent reduction in choriocapillaris development. Subcutaneously administered calcitriol failed to attenuate mouse retinal vasculature development. However, calcitriol and 22-oxacalcitriol administered intraperitoneally, significantly attenuated lesion volume in the laser-induced choroidal neovascularisation mouse model. In summary, calcitriol and 22-oxacalcitriol attenuate ex vivo and in vivo choroidal vasculature angiogenesis. Therefore, vitamin D may have potential as an interventional treatment for ophthalmic neovascular indications.","journal":"Oncotarget","year":2020,"id":87991,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"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":338869,"name":"Bomina Park","orcid":"0000-0003-1440-7066","position":1,"is_corresponding":false},{"id":446835,"name":"Zaheer Ali","orcid":"0000-0002-6505-3096","position":2,"is_corresponding":false},{"id":446836,"name":"Lasse D. Jensen","orcid":"0000-0003-2338-357X","position":3,"is_corresponding":false},{"id":338870,"name":"Timothy W. Corson","orcid":"0000-0002-1402-7875","position":4,"is_corresponding":false},{"id":345358,"name":"Breandán N. Kennedy","orcid":"0000-0001-7991-4689","position":5,"is_corresponding":false},{"id":446834,"name":"Stephanie Merrigan","orcid":"0000-0002-3699-7282","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T22:00:56.736935Z","pmid":"32082484","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":[]}