Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration.

ABSTRACT: Increased vascular leakage and endothelial cell (EC) dysfunction are major features of neurodegenerative diseases. Here, we investigated the mechanisms leading to EC dysregulation and asked whether altered mitochondrial dynamics in ECs impinge on vascular barrier integrity and neurodegeneration. We show that ocular hypertension, a major risk factor to develop glaucoma, induced mitochondrial fragmentation in retinal capillary ECs accompanied by increased oxidative stress and ultrastructural defects. Analysis of EC mitochondrial components revealed overactivation of dynamin-related protein 1 (DRP1), a central regulator of mitochondrial fission, during glaucomatous damage. Pharmacological inhibition or EC-specific in vivo gene delivery of a dominant negative DRP1 mutant was sufficient

SUBMITTER: Cueva-Vargas JL 

PROVIDER: S-EPMC11838204 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature