The aims of the current study were 1: to assess the effect of hyperglycaemia on Edn2 differential expression; 2: to determine whether in Akimba mice the combination of advanced RNV and hyperglycaemia would increase Edn2 expression above that observed in Kimba mice; 3: to establish the cellular localisation of Edn2 in the retinae of these animals deriving further clues to the retinal pathologies in these models; and 4: to assess whether mRNA changes in the retina translate into changes in circulating serum Edn2 protein, an important attribute of a potential biomarker. Here, EDN2 is linked to Hyperglycemia.