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Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1\/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.<\/jats:p>","DOI":"10.3390\/jpm13020291","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T02:57:32Z","timestamp":1675652252000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Systemic Cytokines in Retinopathy of Prematurity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-2252","authenticated-orcid":false,"given":"Po-Yi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Education, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3164-5779","authenticated-orcid":false,"given":"Yuan-Kai","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Education, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rey-In","family":"Lien","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chou","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-7878","authenticated-orcid":false,"given":"Hung-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-7188","authenticated-orcid":false,"given":"Yi-Jen","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-8391","authenticated-orcid":false,"given":"Kuan-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6277-9879","authenticated-orcid":false,"given":"Nan-Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, Columbia University, 622 W 168th St, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Po","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Tucheng Municipal Hospital, New Taipei 236, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2744-3234","authenticated-orcid":false,"given":"Yih-Shiou","family":"Hwang","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Jen-Ai Hospital Dali Branch, Taichung 412, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chun","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung Branch, Keelung 204, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-7255","authenticated-orcid":false,"given":"Wei-Chi","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.survophthal.2018.04.002","article-title":"Retinopathy of prematurity: A review of risk factors and their clinical significance","volume":"63","author":"Kim","year":"2018","journal-title":"Surv. 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