Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration. DOI Creative Commons
Jorge L. Cueva Vargas, Nicolás Belforte, Isaac Alejandro Vidal-Paredes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Increased vascular leakage and endothelial cell (EC) dysfunction are major features of neurodegenerative diseases. Here, we investigated the mechanisms leading to EC dysregulation asked whether altered mitochondrial dynamics in ECs impinge on barrier integrity neurodegeneration. We show that ocular hypertension, a risk factor develop glaucoma, induced fragmentation retinal capillary accompanied by increased oxidative stress ultrastructural defects. Analysis components revealed overactivation dynamin-related protein 1 (DRP1), central regulator fission, during glaucomatous damage. Pharmacological inhibition or EC-specific vivo gene delivery dominant negative DRP1 mutant was sufficient rescue volume, reduce leakage, increase expression tight junction claudin-5 (CLDN5). further demonstrate EC-targeted CLDN5 augmentation restored blood-retinal-barrier integrity, promoted neuronal survival, improved light-evoked visual behaviors mice. Our findings reveal preserving homeostasis function valuable strategies enhance neuroprotection improve vision glaucoma.

Language: Английский

Cadherin 4 assembles a family of color-preferring retinal circuits that respond to light offset DOI

Aline Giselle Rangel Olguin,

Pierre‐Luc Rochon,

Catherine Theriault

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration. DOI Creative Commons
Jorge L. Cueva Vargas, Nicolás Belforte, Isaac Alejandro Vidal-Paredes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Increased vascular leakage and endothelial cell (EC) dysfunction are major features of neurodegenerative diseases. Here, we investigated the mechanisms leading to EC dysregulation asked whether altered mitochondrial dynamics in ECs impinge on barrier integrity neurodegeneration. We show that ocular hypertension, a risk factor develop glaucoma, induced fragmentation retinal capillary accompanied by increased oxidative stress ultrastructural defects. Analysis components revealed overactivation dynamin-related protein 1 (DRP1), central regulator fission, during glaucomatous damage. Pharmacological inhibition or EC-specific vivo gene delivery dominant negative DRP1 mutant was sufficient rescue volume, reduce leakage, increase expression tight junction claudin-5 (CLDN5). further demonstrate EC-targeted CLDN5 augmentation restored blood-retinal-barrier integrity, promoted neuronal survival, improved light-evoked visual behaviors mice. Our findings reveal preserving homeostasis function valuable strategies enhance neuroprotection improve vision glaucoma.

Language: Английский

Citations

0