The validity of A2AR signaling as a promising and novel therapeutic target is supported by rapid (minutes) local increase of adenosine level associated with upregulation of enzymes responsible for generating and maintaining adenosine concentration and delayed (~ 24 h) upregulation of A2AR in oxygen-induced retinopathy (OIR) model of ROP (Elsherbiny et al. 2013; Lutty and McLeod 2003; Liu et al. 2017), diabetic retina of rat with proliferative retinopathy (Vindeirinho et al. 2013) and other pathological conditions (Chen et al. 2013; Frick et al. 2009; Schingnitz et al. 2010; Linden 2011). This evidence concerns the gene ADORA2A and retinopathy of prematurity.