CASP1 and Hyperglycemia: Our major findings are as follows: (1) hyperglycemia upregulates caspase-14 expression in human RPE cells, (2) caspase-14 expression impairs RPE barrier function with no effect on its phagocytic function, and (3) caspase-14 knockdown in RPE inhibits hyperglycemia-mediated RPE barrier disruption, activation of caspase-1 and -9, and enhanced apoptosis.