Caffeine preferentially protects against oxygen-induced retinopathy

Shuya Zhang, Rong Zhou, Bo Li, Haiyan Li, Yanyan Wang, Xuejiao Gu, Lingyun Tang, Cun Wang, Dingjuan Zhong, Yuanyuan Ge, Yuqing Huo, Jing Lin, Xiao Ling Liu, Jiang Fan Chen

Research output: Contribution to journalArticle

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Abstract

Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia-induced vaso-obliteration, which suggests a novel protection window by caffeine. At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by adenosine A2A receptor (A2AR)–dependent mechanism, as revealed by combined caffeine and A2AR-knockout treatment. At the hypoxic phase, caffeine reduced microglial activation and enhanced tip cell formation by A2AR-dependent and -independent mechanisms, as combined caffeine and A2AR knockout produced additive and nearly full protection against OIR. Together with clinical use of caffeine in neonates, our demonstration of the selective protection against OIR, effective therapeutic window, adenosine receptor mechanisms, and neuroglial involvement provide the direct evidence of the novel effects of caffeine therapy in the prevention and treatment of ROP.—Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L., Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.

Original languageEnglish (US)
Pages (from-to)3334-3348
Number of pages15
JournalFASEB Journal
Volume31
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Caffeine
Oxygen
Retinopathy of Prematurity
Premature Infants
Therapeutics
Pathologic Neovascularization
Adenosine A2A Receptors
Hyperoxia
Purinergic P1 Receptors
Apnea
Blindness
Vascular Endothelial Growth Factor A
Brain
Demonstrations
Chemical activation
Observation
Newborn Infant
Apoptosis

Keywords

  • Adenosine A2A receptor
  • Neovascularization
  • Retinopathy of prematurity
  • Vaso-obliteration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., ... Chen, J. F. (2017). Caffeine preferentially protects against oxygen-induced retinopathy. FASEB Journal, 31(8), 3334-3348. https://doi.org/10.1096/fj.201601285R

Caffeine preferentially protects against oxygen-induced retinopathy. / Zhang, Shuya; Zhou, Rong; Li, Bo; Li, Haiyan; Wang, Yanyan; Gu, Xuejiao; Tang, Lingyun; Wang, Cun; Zhong, Dingjuan; Ge, Yuanyuan; Huo, Yuqing; Lin, Jing; Liu, Xiao Ling; Chen, Jiang Fan.

In: FASEB Journal, Vol. 31, No. 8, 01.08.2017, p. 3334-3348.

Research output: Contribution to journalArticle

Zhang, S, Zhou, R, Li, B, Li, H, Wang, Y, Gu, X, Tang, L, Wang, C, Zhong, D, Ge, Y, Huo, Y, Lin, J, Liu, XL & Chen, JF 2017, 'Caffeine preferentially protects against oxygen-induced retinopathy', FASEB Journal, vol. 31, no. 8, pp. 3334-3348. https://doi.org/10.1096/fj.201601285R
Zhang S, Zhou R, Li B, Li H, Wang Y, Gu X et al. Caffeine preferentially protects against oxygen-induced retinopathy. FASEB Journal. 2017 Aug 1;31(8):3334-3348. https://doi.org/10.1096/fj.201601285R
Zhang, Shuya ; Zhou, Rong ; Li, Bo ; Li, Haiyan ; Wang, Yanyan ; Gu, Xuejiao ; Tang, Lingyun ; Wang, Cun ; Zhong, Dingjuan ; Ge, Yuanyuan ; Huo, Yuqing ; Lin, Jing ; Liu, Xiao Ling ; Chen, Jiang Fan. / Caffeine preferentially protects against oxygen-induced retinopathy. In: FASEB Journal. 2017 ; Vol. 31, No. 8. pp. 3334-3348.
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abstract = "Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia-induced vaso-obliteration, which suggests a novel protection window by caffeine. At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by adenosine A2A receptor (A2AR)–dependent mechanism, as revealed by combined caffeine and A2AR-knockout treatment. At the hypoxic phase, caffeine reduced microglial activation and enhanced tip cell formation by A2AR-dependent and -independent mechanisms, as combined caffeine and A2AR knockout produced additive and nearly full protection against OIR. Together with clinical use of caffeine in neonates, our demonstration of the selective protection against OIR, effective therapeutic window, adenosine receptor mechanisms, and neuroglial involvement provide the direct evidence of the novel effects of caffeine therapy in the prevention and treatment of ROP.—Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L., Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.",
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AU - Zhou, Rong

AU - Li, Bo

AU - Li, Haiyan

AU - Wang, Yanyan

AU - Gu, Xuejiao

AU - Tang, Lingyun

AU - Wang, Cun

AU - Zhong, Dingjuan

AU - Ge, Yuanyuan

AU - Huo, Yuqing

AU - Lin, Jing

AU - Liu, Xiao Ling

AU - Chen, Jiang Fan

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AB - Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia-induced vaso-obliteration, which suggests a novel protection window by caffeine. At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by adenosine A2A receptor (A2AR)–dependent mechanism, as revealed by combined caffeine and A2AR-knockout treatment. At the hypoxic phase, caffeine reduced microglial activation and enhanced tip cell formation by A2AR-dependent and -independent mechanisms, as combined caffeine and A2AR knockout produced additive and nearly full protection against OIR. Together with clinical use of caffeine in neonates, our demonstration of the selective protection against OIR, effective therapeutic window, adenosine receptor mechanisms, and neuroglial involvement provide the direct evidence of the novel effects of caffeine therapy in the prevention and treatment of ROP.—Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L., Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.

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KW - Neovascularization

KW - Retinopathy of prematurity

KW - Vaso-obliteration

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