Knockdown of ROBO4 by transcriptional regulation of HIF‐1α/SP1 or miR‐125b‐5p/miR‐146a‐5p targeting could reduce the increased monolayer permeability of RPE cells and elevate the decreased tight junction‐related proteins expression induced by hyperglycaemia or hypoxia, similar to the results of previous studies.49, 50, 51 However, Wang et al52 showed that HG alone only minimally affected cell permeability, except adding hypoxic conditions. Here, SP1 is linked to Hyperglycemia.