CATEGORY:
Research
SCREENSHOT:
TITLE:
VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss
CONTENT:
JCI Insight. 2021 Mar 9:143285. doi: 10.1172/jci.insight.143285. Online ahead of print.
ABSTRACT
AbstractMillions of people are affected by hearing loss. When hearing loss is caused by noise or aging, it is often associated with breakdown of the barrier between the cochlea and its blood vessels. Pericytes populate many small vessels in the adult inner ear, however, their role in different forms of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model, we show that loss of pericytes leads to marked changes in vascular structure, resulting in poor blood circulation and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models in combination with exogenous donor pericytes, we show pericytes, signaled by endothelial growth factor isoform A165 (VEGF-A165), vigorously drives new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1 (AAV1)-mediated VEGF-A165 viral vector to pericyte depleted animals regenerated lost pericytes, improved blood supply, reduced loss of sensory hair cells, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for adult hearing and can regenerate cochlear vasculature. The restoration of vascular function in the damaged inner ear with AAV1-mediated VEGF-A165 gene therapy is a new strategy for ameliorating vascular associated hearing disorders, including common forms of age-related hearing loss.
PMID:33690221 | DOI:10.1172/jci.insight.143285
SOURCE:
JCI insight
PUBLISHER:
PMID:
pubmed:33690221
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33690221
DOI:
10.1172/jci.insight.143285
DATE – PUBLISHED:
Wed, 10 Mar 2021 06:00:00 -0500
DATE – DOI:
2021-03-09T17:03:21Z
DATE – ADDED:
03/10/21 10:18PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33690221/
LINK – DOI:
https://doi.org/10.1172/jci.insight.143285
LINK – PUBLISHER:
http://insight.jci.org/articles/view/143285?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-11T03:18:27+00:00, https://www.hearinglosstreatmentreport.com.