Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide. (July 2022)

• Record Type: Journal Article
• Authors: Zhu, Shuyan; Zidan, Asmaa; Pang, Kunpeng; Musayeva, Aytan; Kang, Qianyan; Yin, Jia
• Is Part Of: Experimental eye research. Volume 220(2022)
• Publication Date: 2022-07
• Subjects: Corneal angiogenesis -- Neovascularization -- Calcitonin gene-related peptide -- Neuropeptide -- Trigeminal ganglion neuron -- Corneal innervation; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109125
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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. Highlights: CGRP is expressed by trigeminal ganglion neurons and corneal nerves. CGRP level in the trigeminal ganglion is increased with corneal neovascularization. CGRP is potently pro-angiogenic in the cornea. Blocking signaling of nerve-derived CGRP inhibits corneal angiogenesis.