{"doi":"10.17615/acs1-8g23","title":"Retinal angiogenesis suppression through small molecule activation of p53","abstract":"Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3–mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies.","journal":"UNC Libraries","year":2020,"id":138916,"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":0.9549,"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":320295,"name":"Jayakrishna Ambati","orcid":"0000-0003-1622-6365","position":1,"is_corresponding":false},{"id":601597,"name":"Valeria Cicatiello","orcid":null,"position":2,"is_corresponding":false},{"id":290469,"name":"Laura Tudisco","orcid":null,"position":3,"is_corresponding":false},{"id":601598,"name":"Nidia Claros","orcid":null,"position":4,"is_corresponding":false},{"id":600995,"name":"Younghee Kim","orcid":"0000-0002-4499-3783","position":5,"is_corresponding":false},{"id":600996,"name":"Victor H. Guaiquil","orcid":"0000-0003-0429-7692","position":6,"is_corresponding":false},{"id":601599,"name":"Susan E. Yanni","orcid":null,"position":7,"is_corresponding":false},{"id":320309,"name":"Nagaraj Kerur","orcid":"0000-0001-5040-2129","position":8,"is_corresponding":false},{"id":237950,"name":"Shahin Rafii","orcid":"0000-0001-5605-1067","position":9,"is_corresponding":false},{"id":537897,"name":"Thomas C. M. Lee","orcid":"0000-0001-7067-405X","position":10,"is_corresponding":false},{"id":497284,"name":"William W. Hauswirth","orcid":"0000-0002-3244-4947","position":11,"is_corresponding":false},{"id":25328,"name":"Till Milde","orcid":"0000-0002-7267-1052","position":12,"is_corresponding":false},{"id":277362,"name":"Sai H. Chavala","orcid":"0000-0002-6135-2064","position":13,"is_corresponding":false},{"id":600997,"name":"Sandro De Falco","orcid":"0000-0002-6501-1697","position":14,"is_corresponding":false},{"id":589978,"name":"John S. Penn","orcid":"0000-0001-8070-5841","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:06.651725Z","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":[]}