Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide.
Calcitonin gene-related peptide
Corneal angiogenesis
Corneal innervation
Neovascularization
Neuropeptide
Trigeminal ganglion neuron
Journal
Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
08
12
2021
revised:
08
05
2022
accepted:
18
05
2022
pubmed:
27
5
2022
medline:
22
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG) neurons, play a key role in corneal angiogenesis. In the current study, we examined the role of TG sensory neuron-derived calcitonin gene-related peptide (CGRP) in promoting corneal neovascularization (CNV). We found that CGRP was expressed in the TG and cultured TG neurons. In the cornea, minimal CGRP mRNA was detected and CGRP immunohistochemical staining was exclusively co-localized with corneal nerves, suggesting corneal nerves are likely the source of CGRP in the cornea. In response to intrastromal suture placement and neovascularization in the cornea, CGRP expression was increased in the TG. In addition, we showed that CGRP was potently pro-angiogenic, leading to vascular endothelial cell (VEC) proliferation, migration, and tube formation in vitro and corneal hemangiogenesis and lymphangiogenesis in vivo. In a co-culture system of TG neurons and VEC, blocking CGRP signaling in the conditioned media of TG neurons led to decreased VEC migration and tube formation. More importantly, subconjunctival injection of a CGRP antagonist CGRP8-37 reduced suture-induced corneal hemangiogenesis and lymphangiogenesis in vivo. Taken together, our data suggest that TG sensory neuron and corneal nerve-derived CGRP promotes corneal angiogenesis.
Identifiants
pubmed: 35618042
pii: S0014-4835(22)00205-6
doi: 10.1016/j.exer.2022.109125
pmc: PMC9428938
mid: NIHMS1821382
pii:
doi:
Substances chimiques
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109125Subventions
Organisme : NEI NIH HHS
ID : K08 EY031340
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY004068
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
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