Adenosine A(2A) receptor antagonists act at the hyperoxic phase to confer protection against retinopathy

作者：Zhou, Rong; Zhang, Shuya; Gu, Xuejiao; Ge, Yuanyuan; Zhong, Dingjuan; Zhou, Yuling; Tang, Lingyun; Liu, Xiao-Ling^*; Chen, Jiang-Fan^*

来源：Molecular Medicine, 2018, 24(1): 41.

DOI：10.1186/s10020-018-0038-1

• Retinopathy of prematurity
• Oxygen-induced retinopathy
• Adenosinde A(2A) receptor
• KW6002

Background: Retinopathy of prematurity (ROP) remains a major cause of childhood blindness and current laser photocoagulation and anti VEGF antibody tieatments are associated with reduced peripheial vision and possible delayed development of retinal vasculatures and neurons. In this study, we advanced the transiational potential of adenosine A(2A) receptor (A(2A)R) antagonists as a novel therapeutic strategy for selectively controlling pathological retinal neovascularization in oxygen induced retinopathy (OIR) model of ROP.
Methods: Developing C57BL76 mice were exposed to 75% oxygen from postnatal (P) day 7 to PI2 and to room air from P12 to P17 and tieated with KW6002 or vehicle at different postnatal developmental stages. Retinal vasculanzation was examined by whole mount fluorescence and cross-sectional hematoxylin-eosin staining. Cellular prolifeiation, astrocyte and microglial activation, and tip cell function were investigated by isolectin staining and immunohistochemistry. Apoptosis was analyzed by TUNEL assay. The effects of oxygen exposuie and KW6002 tieatment were analyzed by two-way A NOVA or Kiuskal Wallis test or independent Student's t-test or Mann Whitney U test.
Conclusions: As ROP being a biphasic disease, our identification of the hyperoxic phase as the effective window, together with selective and robust protection against pathological (but not physiological) angiogenesis, elevates A(2A)R antagonists as a novel therapeutic strategy for ROP treatment.

• 出版日期2018-7-31
• 单位温州医科大学