VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss.
JCI Insight
; 6(8)2021 04 22.
Article
in En
| MEDLINE
| ID: mdl-33690221
ABSTRACT
Millions of people are affected by hearing loss. Hearing loss is frequently caused by noise or aging and often associated with loss of pericytes. Pericytes populate the small vessels in the adult cochlea. However, their role in different types of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model and noise-exposed mouse model, we show that loss of pericytes leads to marked changes in vascular structure, in turn leading to vascular degeneration and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models combined with exogenous donor pericytes, we show that pericytes, signaled by VEGF isoform A165 (VEGFA165), vigorously drive new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1-mediated (AAV1-mediated) VEGFA165 viral vector to pericyte-depleted or noise-exposed animals prevented and regenerated lost pericytes, improved blood supply, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for vascular regeneration, vascular stability, and hearing in adults. The restoration of vascular function in the damaged cochlea, including in noise-exposed animals, suggests that VEGFA165 gene therapy could be a new strategy for ameliorating vascular associated hearing disorders.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cochlea
/
Neovascularization, Physiologic
/
Pericytes
/
Vascular Endothelial Growth Factor A
/
Hearing Loss, Noise-Induced
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
JCI Insight
Year:
2021
Document type:
Article
Affiliation country:
United States