Fig 1: Illustration of cGMP’s suggested effect on EPAC2 activity based on data from both rd1 and rd10. In the rd10 model, EPAC2 activity is decreased compared to wt. Therefore, as a speculation, the rd10 model may compensate for the activity loss by expressing more EPAC2 protein over time within the ONL, which was also seen with rd1. The decreased EPAC2 activity could be the result of increasing cGMP levels, which compete with cAMP for the binding of EPAC2. Increased cGMP binding might in turn prevent stimulation of protective pathways, even if the cAMP level would subsequently increase. The up and down arrows indicate an increase or decrease, respectively, of either Rap1 activity or EPAC2 expression.