title: Adenosine receptors and caffeine in retinopathy of prematurity.
abstract: Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants. Notably, cellular responses to hypoxia are characterized by robust increases in extracellular adenosine production and the markedly induced adenosine receptors, which provide a novel target for preferential control of pathological angiogenesis without affecting normal vascular development. Here, we review the experimental evidence in support of adenosine receptor-based therapeutic strategy for ROP, including the aberrant adenosine signaling in oxygen-induced retinopathy and the role of three adenosine receptor subtypes (A1R, A2AR, A2BR) in development and treatment of ROP using oxygen-induced retinopathy models. The clinical and initial animal evidence that implicate the therapeutic effect of caffeine (a non-selective adenosine receptor antagonist) in treatment of ROP are highlighted. Lastly, we discussed the translational potential as well therapeutic advantage of adenosine receptor- and caffeine-based therapy for ROR and possibly other proliferative retinopathy.
authors.affiliation: Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang, China. Electronic address: chenjf555@gmail.com.
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Neonatology, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhenlang
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neonatology, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Neonatology, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.affiliation: State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002110:Caffeine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D010100:Oxygen / Q000633:toxicity; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics*; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D002110:Caffeine; D010100:Oxygen
keywords: Adenosine; Adenosine (A(1), A(2A), A(2B)) receptors; Caffeine; Oxygen-induced retinopathy; Retinopathy of prematurity