The present invention provides novel agents, expression constructs, compositions and methods useful for treating an ocular disease associated with unwanted PPARδ activity through the modulation of PPARδ expression. The PPARδ interference RNA (iRNA) agents, expression constructs encoding such agents, and compositions comprising such agents or constructs are directed against RNA molecules encoding PPARδ. The methods comprise treating an ocular disease associated with unwanted PPARδ activity in a patient in need thereof by administering an effective amount of a pharmaceutical composition comprising a PPARδ iRNA agent or expression construct encoding such agent to the patient to reduce a symptom associated with unwanted PPARδ activity in the patient.