Evaluation of CaMKII as a therapeutic target for the treatment of diabetic macular oedema

Experiments to determine CAMKII phosphorylation upon BK and THR exposure were undertaken in bovine and human RMECs. Western blotting studies identified a time-dependent increase in CaMKII activity upon agonist treatment persisting for up to 24 hours. Hyperglycaemic conditions for 21 days did not have a significant effect on basal or agonist induced CaMKII phosphorylation.

Increased FITC-dextran leakage was observed in bovine RMEC monolayers challenged with BK and THR and these effects could be largely abolished in the presence of the CaMKII inhibitor, KN-93, but not its inactive analogue, KN-92. To investigate the relevance of these findings to DMO, the effects of systemic administration of KN-93 and KN-92 on retinal vascular leakage in streptozotocin-induced diabetic mice were investigated.

These experiments confirmed an important role for CaMKII in mediating retinal vasopermeability responses in the diabetic retina. Taken together, the work in this thesis suggests that CaMKII could represent a novel therapeutic target for DMO treatment, although further studies will be required to confirm this. <br>