TY - JOUR
T1 - Adenosine receptors and caffeine in retinopathy of prematurity
AU - Chen, Jiang Fan
AU - Zhang, Shuya
AU - Zhou, Rong
AU - Lin, Zhenlang
AU - Cai, Xiaohong
AU - Lin, Jing
AU - Huo, Yuqing
AU - Liu, Xiaoling
N1 - Funding Information:
The work by author's lab as described in this review was supported by the Start-up Fund from Wenzhou Medical University (No. 89211010; No. 89212012), National Natural Science Foundation of China (No. 81630040, No. 81600753, No. 81100672) and Zhejiang Provincial Natural Science Foundation Grant (LY12H12007) and by Boston University School of Medicine special research fund DTD 4-30-14.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Adenosine
KW - Adenosine (A, A, A) receptors
KW - Caffeine
KW - Oxygen-induced retinopathy
KW - Retinopathy of prematurity
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U2 - 10.1016/j.mam.2017.01.001
DO - 10.1016/j.mam.2017.01.001
M3 - Review article
C2 - 28088487
AN - SCOPUS:85010943948
SN - 0098-2997
VL - 55
SP - 118
EP - 125
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
ER -