Molecular analysis of the inner blood-retinal-barrier and its dysregulation in diabetes

In diabetic macular oedema (DMO) the dysfunction of these cells contributes to iBRB impairment, yet our understanding of the molecular biology of the iBRB and how this is changed in DMO remains incomplete. In this study, we performed bulk RNA-seq to analyse barrier gene expression in human retinal microvascular endothelial cells (HRMECs) under conditions mimicking key aspects of the diabetic milieu.

We identified key changes in gene expression following long-term high glucose (HG) exposure, compared to short term exposure to VEGF. Furthermore, several over-represented TF-binding sites were found in barrier genes downregulated in hyperglycaemia. Follow-up studies revealed that TCFL5 is a key regulator of barrier gene expression in HRMECs; however, this TF did not mediate the downregulation of barrier genes under HG conditions.