{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:52:40Z","timestamp":1790319160424,"version":"4.1.0"},"reference-count":161,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY031939"],"award-info":[{"award-number":["R01EY031939"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Challenge Grant"],"award-info":[{"award-number":["Challenge Grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and\/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic\/apyrimidinic endonuclease 1\/reduction-oxidation factor 1 (APE1\/Ref-1). The multifunctional protein APE1\/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1\/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1\/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections.<\/jats:p>","DOI":"10.3390\/ijms221910279","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:15:32Z","timestamp":1632514532000},"page":"10279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Inhibition of APE1\/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-411X","authenticated-orcid":false,"given":"Gabriella D.","family":"Hartman","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"Lambert-Cheatham","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-7875","authenticated-orcid":false,"given":"Timothy W.","family":"Corson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40942-017-0084-9","article-title":"Retinal and choroidal angiogenesis: A review of new targets","volume":"3","author":"Cabral","year":"2017","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0039-6257(98)00035-6","article-title":"Ocular neovascularization: An epidemiologic review","volume":"43","author":"Lee","year":"1998","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"892043","DOI":"10.1155\/2015\/892043","article-title":"Ocular angiogenesis","volume":"2015","author":"Dreyfuss","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4103\/0301-4738.100542","article-title":"The worldwide epidemic of diabetic retinopathy","volume":"60","author":"Zheng","year":"2012","journal-title":"Indian J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/pr.2013.205","article-title":"Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010","volume":"74","author":"Blencowe","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1136\/archdischild-2016-310532","article-title":"Epidemiology of blindness in children","volume":"102","author":"Solebo","year":"2017","journal-title":"Arch. Dis Child."},{"key":"ref_8","first-page":"1857","article-title":"Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: A comprehensive review","volume":"10","author":"Yang","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/1874467211205010036","article-title":"APE1\/Ref-1 role in redox signaling: Translational applications of targeting the redox function of the DNA repair\/redox protein APE1\/Ref-1","volume":"5","author":"Kelley","year":"2012","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1089\/ars.2013.5492","article-title":"Human apurinic\/apyrimidinic endonuclease 1","volume":"20","author":"Li","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1016\/S0021-9258(19)69623-7","article-title":"Purification and characterization of an apurinic\/apyrimidinic endonuclease from HeLa cells","volume":"256","author":"Kane","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13459","DOI":"10.1016\/S0021-9258(18)33471-9","article-title":"Human placental apurinic\/apyrimidinic endonuclease. Mechanism of action","volume":"257","author":"Grafstrom","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13455","DOI":"10.1016\/S0021-9258(18)33470-7","article-title":"Human placental apurinic\/apyrimidinic endonuclease. Its isolation and characterization","volume":"257","author":"Shaper","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/j.1460-2075.1992.tb05097.x","article-title":"Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity","volume":"11","author":"Xanthoudakis","year":"1992","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.drudis.2020.10.015","article-title":"The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease","volume":"26","author":"Caston","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mrfmmm.2008.04.008","article-title":"Evolution of the redox function in mammalian apurinic\/apyrimidinic endonuclease","volume":"643","author":"Georgiadis","year":"2008","journal-title":"Mutat. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41698-017-0023-0","article-title":"Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: From bench to clinic","volume":"1","author":"Shah","year":"2017","journal-title":"NPJ Precis. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1021\/bi400179m","article-title":"Inhibition of apurinic\/apyrimidinic endonuclease I\u2019s redox activity revisited","volume":"52","author":"Zhang","year":"2013","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6548","DOI":"10.1093\/emboj\/16.21.6548","article-title":"The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites","volume":"16","author":"Gorman","year":"1997","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1073\/pnas.91.1.23","article-title":"The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains","volume":"91","author":"Xanthoudakis","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0921-8777(00)00046-X","article-title":"Going APE over ref-1","volume":"461","author":"Evans","year":"2000","journal-title":"Mutat Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/carcin\/19.3.525","article-title":"Deletion analysis of human AP-endonuclease: Minimum sequence required for the endonuclease activity","volume":"19","author":"Izumi","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1128\/MCB.01337-08","article-title":"APE1\/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process","volume":"29","author":"Vascotto","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6520","DOI":"10.1021\/bi500676p","article-title":"High-resolution crystal structures reveal plasticity in the metal binding site of apurinic\/apyrimidinic endonuclease I","volume":"53","author":"He","year":"2014","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkab314","article-title":"Mol* Viewer: Modern web app for 3D visualization and analysis of large biomolecular structures","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acid. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1021\/bi201034z","article-title":"Characterization of the redox activity and disulfide bond formation in apurinic\/apyrimidinic endonuclease","volume":"51","author":"Luo","year":"2012","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lee, Y.R., Joo, H.K., and Jeon, B.H. (2020). The biological role of apurinic\/apyrimidinic endonuclease1\/redox factor-1 as a therapeutic target for vascular inflammation and as a serologic biomarker. Biomedicines, 8.","DOI":"10.3390\/biomedicines8030057"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.redox.2014.01.023","article-title":"Inhibition of APE1\/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization","volume":"2","author":"Li","year":"2014","journal-title":"Redox Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/sj.cdd.4400639","article-title":"Evidence that the bifunctional redox factor \/ AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina","volume":"7","author":"Chiarini","year":"2000","journal-title":"Cell Death Differ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.visres.2010.10.008","article-title":"Inhibition of APE1\/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo","volume":"51","author":"Jiang","year":"2011","journal-title":"Vis. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lee, Y.R., Joo, H.K., Lee, E.O., Park, M.S., Cho, H.S., Kim, S., Jin, H., Jeong, J.O., Kim, C.S., and Jeon, B.H. (2020). Plasma APE1\/Ref-1 correlates with atherosclerotic inflammation in ApoE(\u2212\/\u2212) mice. Biomedicines, 8.","DOI":"10.3390\/biomedicines8090366"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jin, S.A., Lim, B.K., Seo, H.J., Kim, S.K., Ahn, K.T., Jeon, B.H., and Jeong, J.O. (2017). Elevation of serum APE1\/Ref-1 in experimental murine myocarditis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122664"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lee, Y.R., Joo, H.K., Lee, E.O., Cho, H.S., Choi, S., Kim, C.S., and Jeon, B.H. (2019). ATP binding cassette transporter A1 is involved in extracellular secretion of acetylated APE1\/Ref-1. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133178"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s10637-020-00962-x","article-title":"Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors","volume":"39","author":"Eads","year":"2021","journal-title":"Invest. New Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/mc.22313","article-title":"Inhibitors of the apurinic\/apyrimidinic endonuclease 1 (APE1)\/nucleophosmin (NPM1) interaction that display anti-tumor properties","volume":"55","author":"Poletto","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4068\/cmj.2016.52.2.75","article-title":"Dynamic regulation of APE1\/Ref-1 as a therapeutic target protein","volume":"52","author":"Choi","year":"2016","journal-title":"Chonnam. Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cardoso, A.A., Jiang, Y., Luo, M., Reed, A.M., Shahda, S., He, Y., Maitra, A., Kelley, M.R., and Fishel, M.L. (2012). APE1\/Ref-1 regulates STAT3 transcriptional activity and APE1\/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047462"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.exphem.2010.08.011","article-title":"Inhibition of the redox function of APE1\/Ref-1 in myeloid leukemia cell lines results in a hypersensitive response to retinoic acid-induced differentiation and apoptosis","volume":"38","author":"Fishel","year":"2010","journal-title":"Exp. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1074\/jbc.M114.621995","article-title":"Apurinic\/apyrimidinic endonuclease\/redox factor-1 (APE1\/Ref-1) redox function negatively regulates NRF2","volume":"290","author":"Fishel","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1158\/1535-7163.MCT-11-0107","article-title":"Impact of APE1\/Ref-1 redox inhibition on pancreatic tumor growth","volume":"10","author":"Fishel","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1021\/bi101248s","article-title":"Interactions of apurinic\/apyrimidinic endonuclease with a redox inhibitor: Evidence for an alternate conformation of the enzyme","volume":"50","author":"Su","year":"2011","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1089\/ars.2008.2120","article-title":"Role of the multifunctional DNA repair and redox signaling protein Ape1\/Ref-1 in cancer and endothelial cells: Small-molecule inhibition of the redox function of Ape1","volume":"10","author":"Luo","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"ref_43","first-page":"379","article-title":"Apurinic\/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages","volume":"31","author":"Jedinak","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1124\/jpet.118.248088","article-title":"Ref-1\/APE1 inhibition with novel small molecules blocks ocular neovascularization","volume":"367","author":"Sishtla","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1124\/jpet.116.235283","article-title":"Identification and characterization of new chemical entities targeting apurinic\/apyrimidinic endonuclease 1 for the prevention of chemotherapy-induced peripheral neuropathy","volume":"359","author":"Kelley","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1089\/ars.2010.3410","article-title":"Functional analysis of novel analogues of E3330 that block the redox signaling activity of the multifunctional AP endonuclease\/redox signaling enzyme APE1\/Ref-1","volume":"14","author":"Kelley","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1016\/j.bmc.2017.01.028","article-title":"Inhibitors of nuclease and redox activity of apurinic\/apyrimidinic endonuclease 1\/redox effector factor 1 (APE1\/Ref-1)","volume":"25","author":"Laev","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acs.jmedchem.6b00975","article-title":"The essential medicinal chemistry of curcumin","volume":"60","author":"Nelson","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1021\/jm9014857","article-title":"Design and synthesis of novel quinone inhibitors targeted to the redox function of apurinic\/apyrimidinic endonuclease 1\/redox enhancing factor-1 (Ape1\/ref-1)","volume":"53","author":"Nyland","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13759","DOI":"10.1038\/s41598-018-32034-9","article-title":"Blocking HIF signaling via novel inhibitors of CA9 and APE1\/Ref-1 dramatically affects pancreatic cancer cell survival","volume":"8","author":"Logsdon","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13046-021-02046-x","article-title":"Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: Exploiting this novel finding as a potential target","volume":"40","author":"Gampala","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"810","DOI":"10.4049\/jimmunol.160.2.810","article-title":"Nuclear targeted suppression of NF-kappa B activity by the novel quinone derivative E3330","volume":"160","author":"Hiramoto","year":"1998","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.stem.2018.10.013","article-title":"Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis","volume":"23","author":"Cai","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.csbj.2019.02.007","article-title":"Distinct APE1 activities affect the regulation of VEGF transcription under hypoxic conditions","volume":"17","author":"Li","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1167\/iovs.14-14451","article-title":"Suppression of choroidal neovascularization through inhibition of APE1\/Ref-1 redox activity","volume":"55","author":"Li","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/1878-0261.12138","article-title":"APE1\/Ref-1 knockdown in pancreatic ductal adenocarcinoma\u2014Characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing","volume":"11","author":"Shah","year":"2017","journal-title":"Mol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.18632\/oncotarget.23493","article-title":"APE1\/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells","volume":"9","author":"McIlwain","year":"2018","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"453","DOI":"10.14336\/AD.2017.1130","article-title":"APX3330 promotes neurorestorative effects after stroke in type one diabetic rats","volume":"9","author":"Tao","year":"2018","journal-title":"Aging Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.1038\/s41388-018-0388-8","article-title":"Exposure of Barrett\u2019s and esophageal adenocarcinoma cells to bile acids activates EGFR-STAT3 signaling axis via induction of APE1","volume":"37","author":"Bhat","year":"2018","journal-title":"Oncogene"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Cesaratto, L., Codarin, E., Vascotto, C., Leonardi, A., Kelley, M.R., Tiribelli, C., and Tell, G. (2013). Specific inhibition of the redox activity of APE1\/Ref-1 by E3330 blocks TNF-alpha-induced activation of IL-8 production in liver cancer cell lines. PLoS ONE, 8.","DOI":"10.1371\/annotation\/a610ee5c-525c-4d3c-b6b7-a4cde7b8db54"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101970","DOI":"10.1016\/j.redox.2021.101970","article-title":"Activation of NRF2 by APE1\/REF1 is redox-dependent in Barrett\u2019s related esophageal adenocarcinoma cells","volume":"43","author":"Sriramajayam","year":"2021","journal-title":"Redox Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kelley, M.R., Shahda, S., Lakhani, N.J., O\u2019Neil, B., Chu, L., Anderson, A.K., Wan, J., Mosley, A.L., Liu, H., and Messmann, R.A. (2019, January 26\u201330). A phase I study targeting the APE1\/Ref-1 DNA repair-redox signaling protein with the APX3330 inhibitor [abstract]. Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, MA, USA.","DOI":"10.1158\/1535-7163.TARG-19-PR01"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/78496","article-title":"High-performance affinity beads for identifying drug receptors","volume":"18","author":"Shimizu","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102675","DOI":"10.1016\/j.dnarep.2019.102675","article-title":"Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway","volume":"82","author":"Codrich","year":"2019","journal-title":"DNA Repair"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1089\/ars.2008.2198","article-title":"Transcriptional regulatory functions of mammalian AP-endonuclease (APE1\/Ref-1), an essential multifunctional protein","volume":"11","author":"Bhakat","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_66","first-page":"3510","article-title":"Apurinic\/apyrimidinic endonuclease activity is elevated in human adult gliomas","volume":"7","author":"Bobola","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1128\/MCB.20.1.402-415.2000","article-title":"Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha","volume":"20","author":"Carrero","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_68","first-page":"824","article-title":"Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1\/Ref-1 in prostate cancer","volume":"7","author":"Kelley","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0360-3016(00)01561-3","article-title":"Nuclear expression of human apurinic\/apyrimidinic endonuclease (HAP1\/Ref-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome","volume":"50","author":"Koukourakis","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_70","first-page":"4041","article-title":"Prognostic significance of Ape1\/Ref-1 subcellular localization in non-small cell lung carcinomas","volume":"21","author":"Puglisi","year":"2001","journal-title":"Anticancer Res."},{"key":"ref_71","first-page":"2220","article-title":"Altered expression of Ape1\/Ref-1 in germ cell tumors and overexpression in NT2 cells confers resistance to bleomycin and radiation","volume":"61","author":"Robertson","year":"2001","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.mam.2007.04.005","article-title":"The DNA base excision repair protein Ape1\/Ref-1 as a therapeutic and chemopreventive target","volume":"28","author":"Fishel","year":"2007","journal-title":"Mol. Aspects Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.2217\/fon.14.60","article-title":"Targeting DNA repair pathways for cancer treatment: What\u2019s new?","volume":"10","author":"Kelley","year":"2014","journal-title":"Future Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1158\/1535-7163.MCT-16-0253","article-title":"Regulation of HIF1alpha under hypoxia by APE1\/Ref-1 impacts CA9 expression: Dual targeting in patient-derived 3D pancreatic cancer models","volume":"15","author":"Logsdon","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3109\/07357907.2010.512816","article-title":"Reduced expression of DNA repair and redox signaling protein APE1\/Ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression","volume":"28","author":"Jiang","year":"2010","journal-title":"Cancer Invest."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fnut.2015.00010","article-title":"Exploiting base excision repair to improve therapeutic approaches for pancreatic cancer","volume":"2","author":"Sharbeen","year":"2015","journal-title":"Front. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1038\/s41416-021-01270-8","article-title":"Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours","volume":"124","author":"Gampala","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_78","first-page":"133","article-title":"APE1\/Ref-1 as a novel target for retinal diseases","volume":"2","author":"Heisel","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/jcp.21666","article-title":"The Ape-1\/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: Therapeutic implications in tumor angiogenesis","volume":"219","author":"Zou","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8701","DOI":"10.1038\/s41598-018-27025-9","article-title":"Therapeutic positioning of secretory acetylated APE1\/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1200\/JCO.2019.37.15_suppl.3097","article-title":"A phase I study of the APE1 protein inhibitor APX3330 in patients with advanced solid tumors","volume":"37","author":"Shahda","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0197-4580(02)00229-4","article-title":"Is DNA repair compromised in Alzheimer\u2019s disease?","volume":"24","author":"Davydov","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neulet.2009.09.039","article-title":"APE1\/Ref-1 in Alzheimer\u2019s disease: An immunohistochemical study","volume":"466","author":"Marcon","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1097\/00001756-199808240-00012","article-title":"Immunohistochemical localization of redox factor-1 (Ref-1) in Alzheimer\u2019s hippocampus","volume":"9","author":"Tan","year":"1998","journal-title":"Neuroreport"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12017-002-0038-7","article-title":"DNA base-excision repair enzyme apurinic\/apyrimidinic endonuclease\/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis","volume":"2","author":"Shaikh","year":"2002","journal-title":"Neuromol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/WNR.0000000000000712","article-title":"Ape1 protects against MPP+-induced neurotoxicity through ERK1\/2 signaling in PC12 cells","volume":"28","author":"Kang","year":"2017","journal-title":"Neuroreport"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/ars.2013.5511","article-title":"Apurinic\/apyrimidinic endonuclease 1 upregulation reduces oxidative DNA damage and protects hippocampal neurons from ischemic injury","volume":"22","author":"Leak","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"E3558","DOI":"10.1073\/pnas.1606226113","article-title":"APE1\/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury","volume":"113","author":"Stetler","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kelley, M.R., Jiang, Y., Guo, C., Reed, A., Meng, H., and Vasko, M.R. (2014). Role of the DNA base excision repair protein, APE1 in cisplatin, oxaliplatin, or carboplatin induced sensory neuropathy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106485"},{"key":"ref_90","first-page":"151","article-title":"APE1\/Ref-1\u2014One target with multiple indications: Emerging aspects and new directions","volume":"2","author":"Mijiti","year":"2021","journal-title":"J. Cell. Signal."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/ibd\/izaa161","article-title":"Inhibition of APE1\/Ref-1 redox signaling alleviates intestinal dysfunction and damage to myenteric neurons in a mouse model of spontaneous chronic colitis","volume":"27","author":"Sahakian","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00109-013-0993-5","article-title":"Ocular neovascularization","volume":"91","author":"Campochiaro","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.ophtha.2012.11.003","article-title":"The relationship of atherosclerosis to the 10-year cumulative incidence of age-related macular degeneration: The Beaver Dam studies","volume":"120","author":"Klein","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40662-016-0063-5","article-title":"Epidemiology of age-related macular degeneration (AMD): Associations with cardiovascular disease phenotypes and lipid factors","volume":"3","author":"Pennington","year":"2016","journal-title":"Eye Vis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-3-030-66014-7_4","article-title":"Bruch\u2019s membrane and the choroid in age-related macular degeneration","volume":"1256","author":"Edwards","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ophtha.2019.11.004","article-title":"Consensus nomenclature for reporting neovascular age-related macular degeneration data: Consensus on neovascular age-related macular degeneration nomenclature study group","volume":"127","author":"Spaide","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6513","DOI":"10.1167\/iovs.17-23544","article-title":"Macular degeneration epidemiology: Nature-nurture, lifestyle factors, genetic risk, and gene-environment interactions\u2014The Weisenfeld Award Lecture","volume":"58","author":"Seddon","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/978-3-030-66014-7_12","article-title":"Current management of age-related macular degeneration","volume":"1256","author":"Ung","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/09286580701396720","article-title":"Overview of epidemiologic studies of diabetic retinopathy","volume":"14","author":"Klein","year":"2007","journal-title":"Ophthalmic. Epidemiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMra1005073","article-title":"Diabetic retinopathy","volume":"366","author":"Antonetti","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.yexcr.2017.03.030","article-title":"HIF signalling: The eyes have it","volume":"356","author":"Peet","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.pop.2015.05.005","article-title":"Diabetic retinopathy","volume":"42","author":"Hendrick","year":"2015","journal-title":"Prim. Care"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1002\/jcb.25575","article-title":"Angiogenesis and inflammation crosstalk in diabetic retinopathy","volume":"117","author":"Capitao","year":"2016","journal-title":"J. Cell Biochem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2337\/dc13-2002","article-title":"Ocular anti-VEGF therapy for diabetic retinopathy: The role of VEGF in the pathogenesis of diabetic retinopathy","volume":"37","author":"Simo","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1016\/j.ophtha.2010.08.016","article-title":"Two-year outcomes of the ranibizumab for edema of the macula in diabetes (READ-2) study","volume":"117","author":"Nguyen","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.ophtha.2010.03.045","article-title":"A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: Report 2","volume":"117","author":"Michaelides","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Wallsh, J.O., and Gallemore, R.P. (2021). Anti-VEGF-resistant retinal diseases: A review of the latest treatment options. Cells, 10.","DOI":"10.3390\/cells10051049"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3928\/23258160-20170630-06","article-title":"The epidemiology of retinopathy of prematurity in the United States","volume":"48","author":"Ludwig","year":"2017","journal-title":"Ophthalmic. Surg. Lasers Imaging Retin."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1542\/peds.2004-1413","article-title":"Early Treatment for Retinopathy of Prematurity Cooperative Group, The incidence and course of retinopathy of prematurity: Findings from the Early Treatment for Retinopathy of Prematurity Study","volume":"116","author":"Good","year":"2005","journal-title":"Pediatrics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/BF02830827","article-title":"Retinopathy of prematurity\u2014Risk factors","volume":"71","author":"Gupta","year":"2004","journal-title":"Indian J. Pediatr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S1084-2756(03)00119-2","article-title":"Pathogenesis of retinopathy of prematurity","volume":"8","author":"Smith","year":"2003","journal-title":"Semin. Neonatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/MOP.0b013e3283423f35","article-title":"Current update on retinopathy of prematurity: Screening and treatment","volume":"23","author":"Chen","year":"2011","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.ophtha.2018.05.001","article-title":"A dosing study of bevacizumab for retinopathy of prematurity: Late recurrences and additional treatments","volume":"125","author":"Wallace","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/jamaophthalmol.2020.0334","article-title":"Short-term outcomes after very low-dose intravitreous bevacizumab for retinopathy of prematurity","volume":"138","author":"Wallace","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"ref_117","first-page":"235","article-title":"Anti-vascular endothelial growth factor indications in ocular disease","volume":"59","author":"Cornel","year":"2015","journal-title":"Rom. J. Ophthalmol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/ICU.0000000000000657","article-title":"Age-related macular degeneration therapy: A review","volume":"31","author":"Ammar","year":"2020","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ajo.2011.10.016","article-title":"Incidence of legal blindness from age-related macular degeneration in Denmark: Year 2000 to 2010","volume":"153","author":"Bloch","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.ophtha.2006.05.064","article-title":"Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy","volume":"113","author":"Avery","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ricci, F., Bandello, F., Navarra, P., Staurenghi, G., Stumpp, M., and Zarbin, M. (2020). Neovascular age-related macular degeneration: Therapeutic management and new-upcoming approaches. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218242"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mayocp.2011.10.001","article-title":"The expanding role of vascular endothelial growth factor inhibitors in ophthalmology","volume":"87","author":"Stewart","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.ajo.2015.06.011","article-title":"Intravitreal anti-vascular endothelial growth factor treatment and the risk of thromboembolism","volume":"160","author":"Schlenker","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1053\/j.semperi.2019.05.011","article-title":"Anti-vascular endothelial growth factor intravitreal therapy for retinopathy of prematurity","volume":"43","author":"VanderVeen","year":"2019","journal-title":"Semin. Perinatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ajo.2011.01.053","article-title":"Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration","volume":"152","author":"Day","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Palmer, N., Jacobs, B., Shetty, T., Dimaras, H., Hajrasouliha, A.R., Jusufbegovic, D., and Corson, T.W. (2021). Patient preferences in retinal drug delivery. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98568-7"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.exer.2014.10.002","article-title":"Natural product inhibitors of ocular angiogenesis","volume":"129","author":"Sulaiman","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"38183","DOI":"10.1074\/jbc.M302244200","article-title":"Hypoxia up-regulates prolyl hydroxylase activity: A feedback mechanism that limits HIF-1 responses during reoxygenation","volume":"278","author":"Duplan","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.preteyeres.2015.06.002","article-title":"Molecular pathogenesis of retinal and choroidal vascular diseases","volume":"49","author":"Campochiaro","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1161\/01.RES.0000102937.50486.1B","article-title":"Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1","volume":"93","author":"Kelly","year":"2003","journal-title":"Circ. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.ophtha.2016.04.056","article-title":"Anti-vascular endothelial growth factor agents in the treatment of retinal disease: From bench to bedside","volume":"123","author":"Campochiaro","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Sulaiman, R.S., Merrigan, S., Quigley, J., Qi, X., Lee, B., Boulton, M.E., Kennedy, B., Seo, S.Y., and Corson, T.W. (2016). A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. Sci. Rep., 6.","DOI":"10.1038\/srep25509"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1021\/acs.jmedchem.5b00449","article-title":"Synthesis and biological evaluation of novel homoisoflavonoids for retinal neovascularization","volume":"58","author":"Basavarajappa","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/jop.2015.0049","article-title":"A simple optical coherence tomography quantification method for choroidal neovascularization","volume":"31","author":"Sulaiman","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.visres.2017.02.007","article-title":"Canonical Wnt signaling in diabetic retinopathy","volume":"139","author":"Chen","year":"2017","journal-title":"Vis. Res."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Rubsam, A., Parikh, S., and Fort, P.E. (2018). Role of inflammation in diabetic retinopathy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040942"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1476-4598-12-86","article-title":"The complexity of NF-kappaB signaling in inflammation and cancer","volume":"12","author":"Hoesel","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1038\/sj.onc.1203237","article-title":"The Rel\/NF-kappaB signal transduction pathway: Introduction","volume":"18","author":"Gilmore","year":"1999","journal-title":"Oncogene"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1038\/sj.onc.1209933","article-title":"Transcriptional regulation via the NF-kappaB signaling module","volume":"25","author":"Hoffmann","year":"2006","journal-title":"Oncogene"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Park, M.S., Choi, S., Lee, Y.R., Joo, H.K., Kang, G., Kim, C.S., Kim, S.J., Lee, S.D., and Jeon, B.H. (2016). Secreted APE1\/Ref-1 inhibits TNF-alpha-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor. Sci. Rep., 6.","DOI":"10.1038\/srep23015"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/jcs.00963","article-title":"The JAK\/STAT signaling pathway","volume":"117","author":"Rawlings","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Batliwala, S., Xavier, C., Liu, Y., Wu, H., and Pang, I.H. (2017). Involvement of Nrf2 in ocular diseases. Oxid. Med. Cell Longev., 2017.","DOI":"10.1155\/2017\/1703810"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s00109-021-02069-z","article-title":"Antioxidative effects of polypyrimidine tract-binding protein-associated splicing factor against pathological retinal angiogenesis through promotion of mitochondrial function","volume":"99","author":"Dong","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.exer.2006.03.024","article-title":"Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: The role of reactive oxygen species in diabetic retinopathy","volume":"83","author":"Cui","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"43603","DOI":"10.1155\/2007\/43603","article-title":"Oxidative stress and diabetic retinopathy","volume":"2007","author":"Kowluru","year":"2007","journal-title":"Exp. Diabetes Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.2522\/ptj.20080020","article-title":"Epidemiology of diabetes and diabetes-related complications","volume":"88","author":"Deshpande","year":"2008","journal-title":"Phys. Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1182\/blood-2013-09-512749","article-title":"Oxidative stress in angiogenesis and vascular disease","volume":"123","author":"Kim","year":"2014","journal-title":"Blood"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Park, I.S., Mahapatra, C., Park, J.S., Dashnyam, K., Kim, J.W., Ahn, J.C., Chung, P.S., Yoon, D.S., Mandakhbayar, N., and Singh, R.K. (2020). Revascularization and limb salvage following critical limb ischemia by nanoceria-induced Ref-1\/APE1-dependent angiogenesis. Biomaterials, 242.","DOI":"10.1016\/j.biomaterials.2020.119919"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Kobayashi, E.H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H., Tanaka, N., Moriguchi, T., Motohashi, H., and Nakayama, K. (2016). Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun., 7.","DOI":"10.1038\/ncomms11624"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.biocel.2009.11.009","article-title":"Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K\/Akt","volume":"42","author":"Kim","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.freeradbiomed.2011.04.026","article-title":"Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia-reperfusion injury","volume":"51","author":"Wei","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s00125-013-3093-8","article-title":"NRF2 plays a protective role in diabetic retinopathy in mice","volume":"57","author":"Xu","year":"2014","journal-title":"Diabetologia"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neulet.2015.10.019","article-title":"Unfolded protein response is activated in aged retinas","volume":"609","author":"Lenox","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.intimp.2017.11.021","article-title":"Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2\/HO-1 and NF-kB pathways","volume":"54","author":"Bao","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Piechota, M., Pawlowska, E., Szatkowska, M., Sikora, E., and Kaarniranta, K. (2017). Cellular senescence in age-related macular degeneration: Can autophagy and DNA damage response play a role?. Oxid. Med. Cell Longev., 2017.","DOI":"10.1155\/2017\/5293258"},{"key":"ref_157","first-page":"1073","article-title":"Oral APX3330 treatment reduces L-CNV lesions in a preclinical mouse model and confirms Phase 2 DR\/DME clinical dose with sufficient distribution to human retina using PBPK modeling","volume":"62","author":"Silva","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Fishel, M.L., Cheng, H., Shahda, S., and Kelley, M.R. (2015, January 5\u20139). APX3330 Drug Development for Clinical Trials Targeting APE1\/Ref-1 in Pancreatic Cancer [abstract]. Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, Boston, MA, USA.","DOI":"10.1158\/1535-7163.TARG-15-B167"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/jcp.20110","article-title":"Increased expression of VEGF in retinal pigmented epithelial cells is not sufficient to cause choroidal neovascularization","volume":"201","author":"Oshima","year":"2004","journal-title":"J. Cell Physiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"8919","DOI":"10.1073\/pnas.93.17.8919","article-title":"The redox\/DNA repair protein, Ref-1, is essential for early embryonic development in mice","volume":"93","author":"Xanthoudakis","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_161","unstructured":"Kelley, M.R., and Fishel, M.L. Personal Communication."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:04:25Z","timestamp":1760166265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,24]]},"references-count":161,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910279"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910279","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,24]]}}}