Sustained Upregulation of Endothelial Nox4 Mediates Retinal Vascular Pathology in Type 1 Diabetes.

ABSTRACT: NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in retinal endothelial cells (ECs) and is upregulated under hyperglycemic and hypoxic conditions. However, the role of endothelial Nox4 upregulation in long-term retinal blood vessel damage in diabetic retinopathy (DR) remains undefined. Here, we attempted to address this question using humanized EC-specific Nox4 transgenic (hNox4EC-Tg) and EC-specific Nox4 knockout (Nox4EC-KO) mouse models. Our results show that hNox4EC-Tg mice at age of 10-12 months exhibited increased tortuosity of retinal blood vessels, focal vascular leakage, and acellular capillary formation. In vitro study revealed enhanced apoptosis in brain microvascular ECs derived from hNox4EC-Tg mice, concomitant with increased mitochondrial ROS, elevated

SUBMITTER: Tang X 

PROVIDER: S-EPMC9797318 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature