THE PATHOGENIC EFFECTS OF ENDOTHELIN-2 IN THE RETINA: INTERACTIONS WITH ANGIOTENSIN II AND ALDOSTERONE

Increasing evidence indicates that the vasoactive peptide, endothelin (ET), influences cellular pathology, yet its role in ocular disease and the factors that regulate its actions are not fully understood. It was hypothesized that the ET-2 isoform has detrimental actions in the retina in hypertensive and diabetic retinopathy (DR), both independently and through interactions with the renin-angiotensin aldosterone system and oxidative stress enzymes, NADPH oxidase. The findings of this thesis indicated that ET-2 influences various pathogenic processes in the retina. Further, specific inhibition of the ET receptors, abrogated retinal pathology, highlighting the potential of these approaches for the treatment of DR.