| First Author | Alrashdi SF | Year | 2018 |
| Journal | Am J Pathol | Volume | 188 |
| Issue | 3 | Pages | 805-817 |
| PubMed ID | 29248456 | Mgi Jnum | J:258009 |
| Mgi Id | MGI:6117884 | Doi | 10.1016/j.ajpath.2017.11.009 |
| Citation | Alrashdi SF, et al. (2018) Endothelin-2 Injures the Blood-Retinal Barrier and Macroglial Muller Cells: Interactions with Angiotensin II, Aldosterone, and NADPH Oxidase. Am J Pathol 188(3):805-817 |
| abstractText | Although increasing evidence indicates that endothelin-2 (Edn2) has distinct roles in tissue pathology, including inflammation, glial cell dysfunction, and angiogenesis, its role in the retina and the factors that regulate its actions are not fully understood. We hypothesized that Edn2 damages the blood-retinal barrier (BRB) and that this is mediated by interactions with the renin-angiotensin-aldosterone system and reactive oxygen species derived from NADPH oxidase (Nox). C57BL/6J mice received an intravitreal injection of Edn2 or control vehicle to examine the blood pressure-independent effects of Edn2. Mice administered Edn2 were randomized to receive by intraperitoneal injection treatments that inhibited the Edn type a receptor, Edn type b receptor, angiotensin type 1 receptor, mineralocorticoid receptor, or Nox isoforms 1 to 4. One month later, mice administered Edn2 exhibited breakdown of the BRB with increased vascular leakage, vascular endothelial growth factor expression, and infiltrating macrophages (Ly6C(+)CD45(high)CD11b(+)). Further, macroglial Muller cells, which influence the integrity of the BRB and prevent retinal edema, became gliotic and expressed increased levels of water (aquaporin-4) and ion (Kir4.1) channels. This Edn2-mediated retinopathy was reduced by all treatments. Complementary in vitro studies in cultured Muller cells supported these findings and demonstrated the importance of reactive oxygen species in mediating these events. In conclusion, Edn2 has detrimental effects on the BRB and Muller cells that involve interactions with the renin-angiotensin aldosterone system and Nox1/4. |
