{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:39:00Z","timestamp":1791689940762,"version":"4.3.4"},"reference-count":203,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"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":["R01EY025641"],"award-info":[{"award-number":["R01EY025641"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Under healthy conditions, the cornea is an avascular structure which allows for transparency and optimal visual acuity. Its avascular nature is maintained by a balance of proangiogenic and antiangiogenic factors. An imbalance of these factors can result in abnormal blood vessel proliferation into the cornea. This corneal neovascularization (CoNV) can stem from a variety of insults including hypoxia and ocular surface inflammation caused by trauma, infection, chemical burns, and immunological diseases. CoNV threatens corneal transparency, resulting in permanent vision loss. Mainstay treatments of CoNV have partial efficacy and associated side effects, revealing the need for novel treatments. Numerous natural products and synthetic small molecules have shown potential in preclinical studies in vivo as antiangiogenic therapies for CoNV. Such small molecules include synthetic inhibitors of the vascular endothelial growth factor (VEGF) receptor and other tyrosine kinases, plus repurposed antimicrobials, as well as natural source-derived flavonoid and non-flavonoid phytochemicals, immunosuppressants, vitamins, and histone deacetylase inhibitors. They induce antiangiogenic and anti-inflammatory effects through inhibition of VEGF, NF-\u03baB, and other growth factor receptor pathways. Here, we review the potential of small molecules, both synthetics and natural products, targeting these and other molecular mechanisms, as antiangiogenic agents in the treatment of CoNV.<\/jats:p>","DOI":"10.3390\/molecules25153468","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T07:45:57Z","timestamp":1596440757000},"page":"3468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization"],"prefix":"10.3390","volume":"25","author":[{"given":"Zachary","family":"Barry","sequence":"first","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1440-7066","authenticated-orcid":false,"given":"Bomina","family":"Park","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, 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":"Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","first-page":"264","article-title":"Corneal angiogenic privilege: Angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis)","volume":"104","author":"Azar","year":"2006","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/00055735-200108000-00002","article-title":"Corneal neovascularization","volume":"12","author":"Chang","year":"2001","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_3","unstructured":"World Health Organization (2020, May 29). Blindness and Vision Impairment Prevention. Available online: https:\/\/www.who.int\/blindness\/causes\/priority\/en\/index8.html."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pineda, R. (2020). World corneal blindness. Foundations of Corneal Disease, Springer.","DOI":"10.1007\/978-3-030-25335-6_25"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/ICO.0b013e318201405a","article-title":"Treatments for corneal neovascularization: A review","volume":"30","author":"Gupta","year":"2011","journal-title":"Cornea"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s004170100313","article-title":"Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty","volume":"239","author":"Cursiefen","year":"2001","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.ajo.2005.05.020","article-title":"Deep corneal neovascularization after implantation with intrastromal corneal ring segments","volume":"140","author":"Wagoner","year":"2005","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/j.1755-3768.2008.01312.x","article-title":"Efficacy of intravitreal bevacizumab (Avastin) therapy for early and advanced neovascular age-related macular degeneration","volume":"87","author":"Krebs","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/j.ophtha.2008.02.013","article-title":"The effect of topical bevacizumab on corneal neovascularization","volume":"115","author":"Kim","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5935\/0004-2749.20140054","article-title":"Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization","volume":"77","author":"Ozdemir","year":"2014","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cell.2007.08.021","article-title":"Molecular understanding and modern application of traditional medicines: Triumphs and trials","volume":"130","author":"Corson","year":"2007","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.survophthal.2012.01.007","article-title":"Corneal neovascularization: An anti-VEGF therapy review","volume":"57","author":"Chang","year":"2012","journal-title":"Surv. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"Liang","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1083\/jcb.106.4.1375","article-title":"Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix","volume":"106","author":"Madri","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1038\/nprot.2007.368","article-title":"The mouse cornea micropocket angiogenesis assay","volume":"2","author":"Rogers","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/08820530902800017","article-title":"Review of the ocular angiogenesis animal models","volume":"24","author":"Montezuma","year":"2009","journal-title":"Semin. Ophthalmol."},{"key":"ref_17","first-page":"2510","article-title":"Inhibition of inflammatory corneal angiogenesis by TNP-470","volume":"42","author":"Joussen","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3109\/02713688508999984","article-title":"Drug effects on the neovascularization response to silver nitrate cauterization of the rat cornea","volume":"4","author":"Mahoney","year":"1985","journal-title":"Curr. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.exer.2008.08.013","article-title":"BALB\/c and C57BL6 mouse strains vary in their ability to heal corneal epithelial debridement wounds","volume":"87","author":"Tadvalkar","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10456-009-9160-6","article-title":"Anti-angiogenic tyrosine kinase inhibitors: What is their mechanism of action?","volume":"13","author":"Gotink","year":"2010","journal-title":"Angiogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nrd2380","article-title":"Molecular basis for sunitinib efficacy and future clinical development","volume":"6","author":"Faivre","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ceb.2008.12.012","article-title":"VEGFs and receptors involved in angiogenesis versus lymphangiogenesis","volume":"21","author":"Lohela","year":"2009","journal-title":"Curr. Opin Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1167\/iovs.12-10856","article-title":"Sunitinib inhibits inflammatory corneal lymphangiogenesis","volume":"54","author":"Detry","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ajo.2010.04.024","article-title":"Inhibition of corneal neovascularization by topical bevacizumab (anti-VEGF) and sunitinib (anti-VEGF and anti-PDGF) in an animal model","volume":"150","author":"Javaloy","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/ICO.0b013e3182801645","article-title":"Inhibition of corneal neovascularization by subconjunctival and topical bevacizumab and sunitinib in a rabbit model","volume":"32","author":"Ko","year":"2013","journal-title":"Cornea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1242\/dev.126.14.3047","article-title":"Role of PDGF-B and PDGFR-\u03b2 in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse","volume":"126","author":"Hellstrom","year":"1999","journal-title":"Development"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1167\/iovs.05-1071","article-title":"The role of PDGF receptor inhibitors and PI3-kinase signaling in the pathogenesis of corneal neovascularization","volume":"47","author":"Dell","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1167\/iovs.07-1314","article-title":"Inflammatory corneal (lymph)angiogenesis is blocked by VEGFR-tyrosine kinase inhibitor ZK 261991, resulting in improved graft survival after corneal transplantation","volume":"49","author":"Hos","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1158\/0008-5472.CAN-04-1443","article-title":"BAY 43\u20139006 exhibits broad spectrum oral antitumor activity and targets the RAF\/MEK\/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis","volume":"64","author":"Wilhelm","year":"2004","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1634\/theoncologist.2008-0185","article-title":"Sorafenib for the treatment of unresectable hepatocellular carcinoma","volume":"14","author":"Kane","year":"2009","journal-title":"Oncologist"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1097\/ICO.0b013e31823f8b9c","article-title":"Inhibition of corneal neovascularization in rats by systemic administration of sorafenib","volume":"31","author":"Seo","year":"2012","journal-title":"Cornea"},{"key":"ref_32","first-page":"99","article-title":"SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1\/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types","volume":"59","author":"Fong","year":"1999","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000324994","article-title":"Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization","volume":"47","author":"Keskin","year":"2012","journal-title":"Ophthalmic Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1200\/JCO.2002.20.6.1657","article-title":"Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors","volume":"20","author":"Kuenen","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00417-003-0688-7","article-title":"Suppression of experimental choroidal neovascularization utilizing KDR selective receptor tyrosine kinase inhibitor","volume":"241","author":"Takeda","year":"2003","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yoon, H.J., Woo, J.M., Ji, Y.S., and Yoon, K.C. (2019). Comparison of the therapeutic efficacies of topical rivoceranib and topical bevacizumab in a murine model of corneal neovascularization. Medicina (Kaunas), 55.","DOI":"10.3390\/medicina55110729"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1470-2045(12)70364-9","article-title":"Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: A single-group phase 2 trial","volume":"13","author":"Eisen","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_38","first-page":"220","article-title":"Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization","volume":"7","author":"Onder","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1158\/0008-5472.CAN-05-1182","article-title":"Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells","volume":"66","author":"Konecny","year":"2006","journal-title":"Cancer Res."},{"key":"ref_40","first-page":"85","article-title":"The effects of the novel, reversible epidermal growth factor receptor\/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo","volume":"1","author":"Rusnak","year":"2001","journal-title":"Mol. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/ceo.12500","article-title":"Effects of lapatinib and trastuzumab on vascular endothelial growth factor in experimental corneal neovascularization","volume":"43","author":"Kaya","year":"2015","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_42","unstructured":"Pfizer (2020, May 29). Inlyta (Axitinib) Tablets for Oral Administration. Available online: http:\/\/labeling.pfizer.com\/ShowLabeling.aspx?id=759."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/ceo.13333","article-title":"Topical axitinib is a potent inhibitor of corneal neovascularization","volume":"46","year":"2018","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1158\/1078-0432.CCR-04-2129","article-title":"In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models","volume":"11","author":"Lee","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/ICO.0000000000002012","article-title":"Comparison of the effects of dovitinib and bevacizumab on reducing neovascularization in an experimental rat corneal neovascularization model","volume":"38","author":"Sahan","year":"2019","journal-title":"Cornea"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/02713683.2019.1584320","article-title":"Efficacy of sunitinib, sunitinib-hesperetin, and sunitinib-doxycycline combinations on experimentally-induced corneal neovascularization","volume":"44","author":"Ekim","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fonc.2017.00273","article-title":"Giving drugs a second chance: Overcoming regulatory and financial hurdles in repurposing approved drugs as cancer therapeutics","volume":"7","author":"Hernandez","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jaad.2005.10.004","article-title":"Tetracyclines: Nonantibiotic properties and their clinical implications","volume":"54","author":"Sapadin","year":"2006","journal-title":"J. Am. Acad. Derm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1080\/02713680802245772","article-title":"Inhibitory effect of oral doxycycline on neovascularization in a rat corneal alkali burn model of angiogenesis","volume":"33","author":"Dan","year":"2008","journal-title":"Curr. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1097\/ICO.0b013e3181605ff9","article-title":"Inhibition of experimental angiogenesis of cornea by various doses of doxycycline and combination of triamcinolone acetonide with low-molecular-weight heparin and doxycycline","volume":"27","author":"Aydin","year":"2008","journal-title":"Cornea"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1167\/iovs.12-10323","article-title":"Doxycycline-mediated inhibition of corneal angiogenesis: An MMP-independent mechanism","volume":"54","author":"Su","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.neuint.2006.10.008","article-title":"Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration","volume":"50","author":"Yao","year":"2007","journal-title":"Neurochem. Int."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Xiao, O., Xie, Z.L., Lin, B.W., Yin, X.F., Pi, R.B., and Zhou, S.Y. (2012). Minocycline inhibits alkali burn-induced corneal neovascularization in mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041858"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.1016\/S0924-8579(09)70005-6","article-title":"A review of tigecycline\u2014The first glycylcycline","volume":"32","author":"Peterson","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"452685","DOI":"10.1155\/2014\/452685","article-title":"Inhibition of corneal neovascularization by topical and subconjunctival tigecycline","volume":"2014","author":"Goktas","year":"2014","journal-title":"J. Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1021\/cb600362d","article-title":"Inhibition of angiogenesis by the antifungal drug itraconazole","volume":"2","author":"Chong","year":"2007","journal-title":"ACS Chem. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1159\/000366283","article-title":"Antiangiogenic effect of itraconazole on corneal neovascularization: A pilot experimental investigation","volume":"52","author":"Goktas","year":"2014","journal-title":"Ophthalmic Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1126\/science.3887571","article-title":"Qinghaosu (artemisinin): An antimalarial drug from China","volume":"228","author":"Klayman","year":"1985","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1043-6618(03)00107-5","article-title":"Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro","volume":"48","author":"Chen","year":"2003","journal-title":"Pharm Res."},{"key":"ref_60","first-page":"150","article-title":"Topical dihydroartemisinin inhibits suture-induced neovascularization in rat corneas through ERK1\/2 and p38 pathways","volume":"4","author":"Zhong","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1161\/01.ATV.0000016045.93313.F2","article-title":"Central roles of \u03b15\u03b21 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies","volume":"22","author":"Francis","year":"2002","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.exer.2007.06.004","article-title":"The role of integrin \u03b15\u03b21 in the regulation of corneal neovascularization","volume":"85","author":"Muether","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-pathol-012513-104720","article-title":"Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology","volume":"9","author":"Semenza","year":"2014","journal-title":"Annu. Rev. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1111\/bph.13177","article-title":"Imidazole-based alkaloid derivative LCB54\u20130009 suppresses ocular angiogenesis and lymphangiogenesis in models of experimental retinopathy and corneal neovascularization","volume":"172","author":"Kim","year":"2015","journal-title":"Br. J. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.immunol.14.1.649","article-title":"The NF-\u03baB and I\u03baB proteins: New discoveries and insights","volume":"14","author":"Baldwin","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1167\/iovs.10-6167","article-title":"Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model","volume":"52","author":"Kubota","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1167\/iovs.14-14671","article-title":"I\u03baB kinase-\u03b2 inhibitor IMD-0354 beneficially suppresses retinal vascular permeability in streptozotocin-induced diabetic mice","volume":"55","author":"Lennikov","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10456-018-9594-9","article-title":"Selective IKK2 inhibitor IMD0354 disrupts NF-\u03baB signaling to suppress corneal inflammation and angiogenesis","volume":"21","author":"Lennikov","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_69","first-page":"495704","article-title":"Biological and pharmacological aspects of the NK1-receptor","volume":"2015","author":"Gascon","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_70","first-page":"1423","article-title":"Identification of substance-P as an early inductive cytokine of corneal wound and its possible role in the mobilization of mesenchymal stem cell and corneal wound healing","volume":"45","author":"Son","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6783","DOI":"10.1167\/iovs.14-14553","article-title":"NK1 receptor antagonists as a new treatment for corneal neovascularization","volume":"55","author":"Bignami","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.4049\/jimmunol.165.8.4372","article-title":"CXCR4 receptor expression on human retinal pigment epithelial cells from the blood-retina barrier leads to chemokine secretion and migration in response to stromal cell-derived factor 1 alpha","volume":"165","author":"Crane","year":"2000","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nature08151","article-title":"CCR3 is a target for age-related macular degeneration diagnosis and therapy","volume":"460","author":"Takeda","year":"2009","journal-title":"Nature"},{"key":"ref_74","first-page":"251","article-title":"Inhibitory effect of CCR3 signal on alkali-induced corneal neovascularization","volume":"5","author":"Zhou","year":"2012","journal-title":"Int. J. Ophthalmol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1126\/science.275.5302.964","article-title":"Isolation of putative progenitor endothelial cells for angiogenesis","volume":"275","author":"Asahara","year":"1997","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.it.2007.05.007","article-title":"The SDF-1-CXCR4 signaling pathway: A molecular hub modulating neo-angiogenesis","volume":"28","author":"Petit","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_77","first-page":"44","article-title":"Effects of AMD3100 subconjunctival injection on alkali burn induced corneal neovascularization in mice","volume":"4","author":"Peng","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"29913","DOI":"10.1074\/jbc.M111.226423","article-title":"Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells","volume":"286","author":"Markowska","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/iovs.16-20009","article-title":"Galectin-3 inhibition by a small-molecule inhibitor reduces both pathological corneal neovascularization and fibrosis","volume":"58","author":"Chen","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/348555a0","article-title":"Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth","volume":"348","author":"Ingber","year":"1990","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.1073\/pnas.94.12.6099","article-title":"The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2","volume":"94","author":"Sin","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.1073\/pnas.97.12.6427","article-title":"Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1\/CIP1","volume":"97","author":"Zhang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1021\/np200906s","article-title":"Natural products as sources of new drugs over the 30 years from 1981 to 2010","volume":"75","author":"Newman","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.3390\/nu2121231","article-title":"Chemistry and biochemistry of dietary polyphenols","volume":"2","author":"Tsao","year":"2010","journal-title":"Nutrients"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.4049\/jimmunol.170.8.4335","article-title":"Neutrophil restraint by green tea: Inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis","volume":"170","author":"Dona","year":"2003","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S0024-3205(03)00424-7","article-title":"Green tea extract inhibits angiogenesis of human umbilical vein endothelial cells through reduction of expression of VEGF receptors","volume":"73","author":"Hua","year":"2003","journal-title":"Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.3390\/ijms9061034","article-title":"Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG","volume":"9","author":"Shimizu","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1021\/tx990003t","article-title":"Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (-)-epigallocatechin gallate with peroxyl radicals","volume":"12","author":"Valcic","year":"1999","journal-title":"Chem. Res. Toxicol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/ICO.0000000000000104","article-title":"Effect of topical epigallocatechin gallate on corneal neovascularization in rabbits","volume":"33","author":"Koh","year":"2014","journal-title":"Cornea"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.exer.2004.04.008","article-title":"Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization","volume":"79","author":"Castro","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2147\/IJN.S114754","article-title":"Preparation of arginine-glycine-aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization","volume":"12","author":"Chang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/j.foodchem.2012.11.139","article-title":"A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention","volume":"138","author":"Chen","year":"2013","journal-title":"Food Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1080\/01635580802666281","article-title":"Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells","volume":"61","author":"Luo","year":"2009","journal-title":"Nutr. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Chuang, Y.-L., Fang, H.-W., Ajitsaria, A., Chen, K.-H., Su, C.-Y., Liu, G.-S., and Tseng, C.-L. (2019). Development of kaempferol-loaded gelatin nanoparticles for the treatment of corneal neovascularization in mice. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120635"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/ptr.5348","article-title":"A review: The pharmacology of isoliquiritigenin","volume":"29","author":"Peng","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1136\/bjophthalmol-2011-300110","article-title":"Isoliquiritigenin from licorice root suppressed neovascularisation in experimental ocular angiogenesis models","volume":"95","author":"Jhanji","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1006\/exer.2000.0900","article-title":"Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids","volume":"71","author":"Joussen","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_98","first-page":"4851","article-title":"Genistein exerts multiple suppressive effects on human breast carcinoma cells","volume":"58","author":"Shao","year":"1998","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1021\/acs.jnatprod.5b00198","article-title":"Naringenin inhibits UVB irradiation-induced inflammation and oxidative stress in the skin of hairless mice","volume":"78","author":"Martinez","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jnutbio.2016.03.013","article-title":"The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-\u03baB activation","volume":"33","author":"Zarpelon","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"623509","DOI":"10.1155\/2014\/623509","article-title":"Preparation of naringenin\/\u03b2-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats","volume":"2014","author":"Xu","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.1167\/iovs.16-19702","article-title":"Naringenin eye drops inhibit corneal neovascularization by anti-inflammatory and antioxidant mechanisms","volume":"58","author":"Oguido","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jare.2018.01.002","article-title":"Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review","volume":"11","author":"Das","year":"2018","journal-title":"J. Adv. Res."},{"key":"ref_104","first-page":"1588","article-title":"Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat","volume":"30","author":"Haynes","year":"1989","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0006-2952(83)90569-5","article-title":"In vitro inhibition of the biosynthesis of slow reacting substance of anaphylaxis (SRS-A) and lipoxygenase activity by quercetin","volume":"32","author":"Hope","year":"1983","journal-title":"Biochem. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/0005-2760(83)90106-6","article-title":"Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis","volume":"753","author":"Neichi","year":"1983","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1590\/S0074-02762001000500026","article-title":"Biological activities of Curcuma longa L.","volume":"96","author":"Araujo","year":"2001","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0304-3835(95)03887-3","article-title":"Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds","volume":"95","author":"Menon","year":"1995","journal-title":"Cancer Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/00005373-200111000-00017","article-title":"Protective effects of curcumin against oxidative damage on skin cells in vitro: Its implication for wound healing","volume":"51","author":"Phan","year":"2001","journal-title":"J. Trauma"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3109\/02713680903528345","article-title":"The effect of curcumin on corneal neovascularization in rabbit eyes","volume":"35","author":"Kim","year":"2010","journal-title":"Curr. Eye Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000126081","article-title":"Inhibitory effect of curcumin on corneal neovascularization in vitro and in vivo","volume":"222","author":"Bian","year":"2008","journal-title":"Ophthalmologica"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s00109-015-1277-z","article-title":"Curcumin nanoparticles inhibit corneal neovascularization","volume":"93","author":"Pradhan","year":"2015","journal-title":"J. Mol. Med. (Berl.)"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1002\/ijc.24967","article-title":"The dark side of curcumin","volume":"126","author":"Salvador","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1749-6632.2002.tb02918.x","article-title":"Cancer chemopreventive activity of resveratrol","volume":"957","author":"Bhat","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1096\/fj.01-0028fje","article-title":"Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes","volume":"15","author":"Brakenhielm","year":"2001","journal-title":"FASEB J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.burns.2012.07.018","article-title":"Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn","volume":"39","author":"Doganay","year":"2013","journal-title":"Burns"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10456-004-1026-3","article-title":"Withaferin A is a potent inhibitor of angiogenesis","volume":"7","author":"Mohan","year":"2004","journal-title":"Angiogenesis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.chembiol.2007.04.010","article-title":"The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin","volume":"14","author":"Hamza","year":"2007","journal-title":"Chem. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00436-011-2611-1","article-title":"Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB\/c mice","volume":"110","author":"Chandel","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.phymed.2013.03.006","article-title":"Characterization of xanthatin: Anticancer properties and mechanisms of inhibited murine melanoma in vitro and in vivo","volume":"20","author":"Li","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1080\/14756360500213231","article-title":"Synthesis of reduced xanthatin derivatives and in vitro evaluation of their antifungal activity","volume":"20","author":"Pinel","year":"2005","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_122","first-page":"10355","article-title":"Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells","volume":"8","author":"Yu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_123","first-page":"769","article-title":"Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2 mediated STAT3\/PI3K\/Akt signaling pathway","volume":"42","author":"Shen","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_124","first-page":"2666","article-title":"Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells","volume":"8","author":"Kiviharju","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00126839-200304010-00001","article-title":"Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f","volume":"4","author":"Qiu","year":"2003","journal-title":"Drugs R D"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/ar.23583","article-title":"Triptolide suppresses alkali burn-induced corneal angiogenesis along with a downregulation of VEGFA and VEGFC expression","volume":"300","author":"Wang","year":"2017","journal-title":"Anat. Rec."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1055\/s-2006-957994","article-title":"Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation","volume":"61","author":"Houghton","year":"1995","journal-title":"Planta Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0378-8741(01)00216-1","article-title":"The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa","volume":"76","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/1099-1573(200008)14:5<323::AID-PTR621>3.0.CO;2-Q","article-title":"Antioxidant activity of Nigella sativa essential oil","volume":"14","author":"Burits","year":"2000","journal-title":"Phytother. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.biocel.2005.10.009","article-title":"Thymoquinone: A promising anti-cancer drug from natural sources","volume":"38","author":"Roessner","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1097\/ICO.0b013e31804f5a45","article-title":"Inhibitory effects of topical thymoquinone on corneal neovascularization","volume":"26","author":"Erdurmus","year":"2007","journal-title":"Cornea"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1210\/jc.2003-031545","article-title":"Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes","volume":"89","author":"Zaghetto","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8438101","DOI":"10.1155\/2018\/8438101","article-title":"Inhibitory effects of Glycyrrhiza glabra and its major constituent glycyrrhizin on inflammation-associated corneal neovascularization","volume":"2018","author":"Shah","year":"2018","journal-title":"Evid.-Based Complementary Altern. Med."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Cai, X., Chen, Z., Pan, X., Xia, L., Chen, P., Yang, Y., Hu, H., Zhang, J., Li, K., and Ge, J. (2014). Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: Mechanisms contributing to the SDF-1\/CXCR4 axis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088176"},{"key":"ref_135","first-page":"3206","article-title":"Ligustrazine as a salvage agent for patients with relapsed or refractory non-Hodgkin\u2019s lymphoma","volume":"123","author":"Yang","year":"2010","journal-title":"Chin. Med. J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.bbrc.2007.05.004","article-title":"CXCR4 down-regulation by small interfering RNA inhibits invasion and tubule formation of human retinal microvascular endothelial cells","volume":"358","author":"Yu","year":"2007","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.biopha.2018.10.091","article-title":"Tetramethylpyrazine (TMP) ameliorates corneal neovascularization via regulating cell infiltration into cornea after alkali burn","volume":"109","author":"Wu","year":"2019","journal-title":"Biomed. Pharm."},{"key":"ref_138","first-page":"168","article-title":"Understanding the mechanisms of action of methotrexate","volume":"65","author":"Tian","year":"2007","journal-title":"Bull. NYU Hosp. Jt. Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1254\/jjp.48.499","article-title":"Effect of methotrexate on local cerebral blood flow in conscious rats","volume":"48","author":"Mizusawa","year":"1988","journal-title":"Jpn. J. Pharm."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/IAE.0b013e3181e46ad8","article-title":"The effect of methotrexate on corneal neovascularization in rabbits","volume":"30","author":"Byun","year":"2011","journal-title":"Cornea"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1007\/s004170050387","article-title":"Topical application of methotrexate for inhibition of corneal angiogenesis","volume":"237","author":"Joussen","year":"1999","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_142","first-page":"1640","article-title":"Chromatographic separation of racemic thalidomide and teratogenic activity of its enantiomers (author\u2019s transl)","volume":"29","author":"Blaschke","year":"1979","journal-title":"Arzneimittelforschung"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1007\/s004170050330","article-title":"Effect of thalidomide and structurally related compounds on corneal angiogenesis is comparable to their teratological potency","volume":"237","author":"Joussen","year":"1999","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s004170050106","article-title":"Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor","volume":"236","author":"Kruse","year":"1998","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"17131","DOI":"10.1038\/s41598-018-35457-6","article-title":"Understanding the thalidomide chirality in biological processes by the self-disproportionation of enantiomers","volume":"8","author":"Tokunaga","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.4049\/jimmunol.161.8.4236","article-title":"CC-3052: A water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-\u03b1 production","volume":"161","author":"Marriott","year":"1998","journal-title":"J. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1097\/ICO.0b013e318292a79d","article-title":"The inhibitory effect of thalidomide analogue on corneal neovascularization in rabbits","volume":"32","author":"Lee","year":"2013","journal-title":"Cornea"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1158\/1535-7163.MCT-05-0254","article-title":"A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities","volume":"5","author":"Li","year":"2006","journal-title":"Mol. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1167\/iovs.18-24015","article-title":"Therapeutic effects of a novel phenylphthalimide analog for corneal neovascularization and retinal vascular leakage","volume":"59","author":"Wang","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1016\/S0968-0896(02)00152-9","article-title":"Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues","volume":"10","author":"Lima","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1183\/09031936.03.00108603","article-title":"Therapeutic potential of a new phosphodiesterase inhibitor in acute lung injury","volume":"22","author":"Rocco","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000337137","article-title":"Potential inhibitory effect of LASSBio-596, a new thalidomide hybrid, on inflammatory corneal angiogenesis in rabbits","volume":"48","author":"Ribeiro","year":"2012","journal-title":"Ophthalmic Res."},{"key":"ref_153","first-page":"274","article-title":"Corneal neovascularization induced by xenografts or chemical cautery. Inhibition by cyclosporin A","volume":"38","author":"Benelli","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1007\/s00417-013-2467-4","article-title":"Inhibitory effects of topical cyclosporine A 0.05% on immune-mediated corneal neovascularization in rabbits","volume":"251","author":"Bucak","year":"2013","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.survophthal.2011.05.003","article-title":"Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease","volume":"56","author":"Durrani","year":"2011","journal-title":"Surv. Ophthalmol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.exer.2016.04.016","article-title":"Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers\u2014An alternative mode of therapy","volume":"147","author":"Cejkova","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1097\/00007890-199904150-00017","article-title":"Sirolimus (rapamycin)-based therapy in human renal transplantation: Similar efficacy and different toxicity compared with cyclosporine 1, 2","volume":"67","author":"Groth","year":"1999","journal-title":"Transplantation"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/bjc.2012.399","article-title":"Biomarkers: The next therapeutic hurdle in metastatic renal cell carcinoma","volume":"107","author":"Sonpavde","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1167\/iovs.04-0753","article-title":"Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo","volume":"46","author":"Kwon","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1167\/iovs.13-11684","article-title":"Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-\u03b21\/ERK pathways regulation","volume":"54","author":"Shin","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_161","first-page":"97","article-title":"The effects of topical everolimus and sunitinib on corneal neovascularization","volume":"35","author":"Ergin","year":"2016","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.7164\/antibiotics.40.1249","article-title":"FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics","volume":"40","author":"Kino","year":"1987","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/02713683.2010.516620","article-title":"The impact of tacrolimus on vascular endothelial growth factor in experimental corneal neovascularization","volume":"36","author":"Turgut","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/ICO.0000000000000336","article-title":"Comparative study of tacrolimus and bevacizumab on corneal neovascularization in rabbits","volume":"34","author":"Park","year":"2015","journal-title":"Cornea"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1385\/MO:22:2:129","article-title":"In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7","volume":"22","author":"Roomi","year":"2005","journal-title":"Med. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1007\/s00417-007-0542-4","article-title":"Inhibition of corneal angiogenesis by ascorbic acid in the rat model","volume":"245","author":"Peyman","year":"2007","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1097\/ICO.0b013e318241433b","article-title":"Treatment of corneal neovascularization by topical application of ascorbic acid in the rabbit model","volume":"31","author":"Lee","year":"2012","journal-title":"Cornea"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1055\/s-2005-857950","article-title":"A new treatment of keratectasia after LASIK by using collagen with riboflavin\/UVA light cross-linking","volume":"222","author":"Kohlhaas","year":"2005","journal-title":"Klin. Mon. Augenheilkd."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","article-title":"Riboflavin\/ultraviolet-A\u2013induced collagen crosslinking for the treatment of keratoconus","volume":"135","author":"Wollensak","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/ICO.0b013e3180334f78","article-title":"Safety of UVA-riboflavin cross-linking of the cornea","volume":"26","author":"Spoerl","year":"2007","journal-title":"Cornea"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1111\/ajt.14874","article-title":"UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival","volume":"18","author":"Hou","year":"2018","journal-title":"Am. J. Transpl."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0161-6420(02)01998-X","article-title":"Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial\u2014VIP report no. 3","volume":"110","author":"Blinder","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbcan.2012.03.003","article-title":"Angiogenesis inhibition for the improvement of photodynamic therapy: The revival of a promising idea","volume":"1826","author":"Weiss","year":"2012","journal-title":"Biochim. Biophys. Acta-Rev. Cancer"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5862","DOI":"10.1167\/iovs.17-22904","article-title":"Photodynamic therapy leads to time-dependent regression of pathologic corneal (lymph) angiogenesis and promotes high-risk corneal allograft survival","volume":"58","author":"Hou","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_175","first-page":"83","article-title":"Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma","volume":"36","author":"Shokravi","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"493","DOI":"10.18632\/oncotarget.27380","article-title":"Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis ex vivo and in vivo","volume":"11","author":"Merrigan","year":"2020","journal-title":"Oncotarget"},{"key":"ref_177","first-page":"154","article-title":"Effects of 1\u03b1, 25-dihydroxyvitamin D3 on Langerhans cell migration and corneal neovascularization in mice","volume":"41","author":"Suzuki","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1161\/ATVBAHA.108.172528","article-title":"VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating matrix metalloproteinase expression and angiogenesis","volume":"28","author":"Ha","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1039\/c2np00066k","article-title":"Largazole: From discovery to broad-spectrum therapy","volume":"29","author":"Hong","year":"2012","journal-title":"Nat. Prod. Rep."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.ejphar.2014.06.019","article-title":"Largazole, an inhibitor of class I histone deacetylases, attenuates inflammatory corneal neovascularization","volume":"740","author":"Zhou","year":"2014","journal-title":"Eur. J. Pharm."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1139\/cjpp-2014-0117","article-title":"Suberoylanilide hydroxamic acid suppresses inflammation-induced neovascularization","volume":"92","author":"Zhou","year":"2014","journal-title":"Can. J. Physiol. Pharm."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1021\/mp300445a","article-title":"Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model","volume":"10","author":"Li","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1039\/C8MD90019A","article-title":"What are the drugs of the future?","volume":"9","author":"Ngo","year":"2018","journal-title":"MedChemComm"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nrd3746","article-title":"Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars","volume":"11","author":"Berkowitz","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Sugiki, T., Furuita, K., Fujiwara, T., and Kojima, C. (2018). Current NMR Techniques for structure-based drug discovery. Molecules, 23.","DOI":"10.3390\/molecules23010148"},{"key":"ref_186","first-page":"367","article-title":"Noninvasive routes of proteins and peptides drug delivery","volume":"73","author":"Jitendra","year":"2011","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular drug delivery","volume":"12","author":"Gaudana","year":"2010","journal-title":"AAPS J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1089\/jop.2012.0200","article-title":"Novel strategies for anterior segment ocular drug delivery","volume":"29","author":"Cholkar","year":"2013","journal-title":"J. Ocul. Pharm."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0939-6411(03)00138-3","article-title":"Cyclosporine A delivery to the eye: A pharmaceutical challenge","volume":"56","author":"Lallemand","year":"2003","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.canlet.2008.04.014","article-title":"Multitargeted therapy of cancer by green tea polyphenols","volume":"269","author":"Khan","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"14513","DOI":"10.1007\/s13277-016-5364-8","article-title":"Natural products against cancer angiogenesis","volume":"37","author":"Rahman","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_192","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_193","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_194","first-page":"556","article-title":"Inhibition of choroidal neovascularization by homoisoflavanone, a new angiogenesis inhibitor","volume":"14","author":"Kim","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.bbrc.2007.08.100","article-title":"Homoisoflavanone inhibits retinal neovascularization through cell cycle arrest with decrease of cdc2 expression","volume":"362","author":"Kim","year":"2007","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"7673","DOI":"10.1039\/C4OB01604A","article-title":"The first synthesis of the antiangiogenic homoisoflavanone, cremastranone","volume":"12","author":"Lee","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep25509","article-title":"A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy","volume":"6","author":"Sulaiman","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"786","DOI":"10.15252\/emmm.201606561","article-title":"Ferrochelatase is a therapeutic target for ocular neovascularization","volume":"9","author":"Basavarajappa","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Pran Babu, S.P.S., White, D., and Corson, T.W. (2020). Ferrochelatase regulates retinal neovascularization. FASEB J.","DOI":"10.1096\/fj.202000964R"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Shetty, T., and Corson, T.W. (2020). Mitochondrial heme synthesis enzymes as therapeutic targets in vascular diseases. Front. Pharm.","DOI":"10.3389\/fphar.2020.01015"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1021\/acschembio.7b00854","article-title":"Chemical proteomics reveals soluble epoxide hydrolase as a therapeutic target for ocular neovascularization","volume":"13","author":"Sulaiman","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fphar.2019.00095","article-title":"Soluble epoxide hydrolase inhibition for ocular diseases: Vision for the future","volume":"10","author":"Park","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s00417-011-1709-6","article-title":"Combination of vascular endothelial growth factor receptor\/platelet-derived growth factor receptor inhibition markedly improves the antiangiogenic efficacy for advanced stage mouse corneal neovascularization","volume":"249","author":"Chaoran","year":"2011","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/15\/3468\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:59Z","timestamp":1760176379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/15\/3468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":203,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["molecules25153468"],"URL":"https:\/\/doi.org\/10.3390\/molecules25153468","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,30]]}}}