The role of sensory innervation in cornea‐lens regeneration

• Published in: Developmental dynamics Vol. 248; no. 7; pp. 530 - 544
• Main Authors: Perry, Kimberly J., Hamilton, Paul W., Sonam, Surabhi, Singh, Ratnakar, Henry, Jonathan J.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.07.2019; Wiley Subscription Services, Inc
• Subjects: Animals; Attenuation; Capsaicin; Cornea; Cornea - innervation; Cornea - physiology; Critical components; denervation; Epithelium; Homeostasis; Innervation; lens regeneration; Lens, Crystalline - innervation; Lens, Crystalline - physiology; Lenses; Nerves; Neuropeptides; Neurotrophic factors; nociceptors; Reduction; Regeneration; Regeneration (physiology); Regeneration - drug effects; Sensory neurons; Sensory Receptor Cells - physiology; Signal Transduction; Substance P; Substance P - analogs & derivatives; Substance P - pharmacology; Trigeminal nerve; Trigeminal Nerve Injuries; Xenopus; Xenopus laevis; Xenopus; nociceptors; lens regeneration; denervation; Substance P; cornea; capsaicin
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.42

Background Numerous sensory nerves in the cornea contribute to normal tissue homeostasis. Interestingly, cells within the basal corneal epithelium can regenerate new lenses in the frog, Xenopus. In this study, we investigated whether cornea sensory nerves or their neuropeptides are important for supporting cornea‐lens regeneration. Results Attempts to sever the trigeminal nerve trunk, which provides sensory nerve branches to the cornea, did not inhibit lens regeneration. However, using this approach we found that it was not possible to completely disrupt sensory innervation, as these nerves are able to quickly regenerate back to the cornea. On the other hand, attenuation of neuropeptide levels with capsaicin was found to significantly inhibit lens regeneration, as visualized by a reduction of Substance P. These treatments also led to a reduction of cornea sensory innervation. Interestingly, inhibition of the Substance P‐preferred receptor NK‐1 with Spantide II did not affect lens‐regeneration rates. Conclusions This study provides evidence that cornea nerves support cornea‐lens regeneration, which could occur through the release of various neurotrophic factors. Substance P, however, does not appear to be the critical component of this signaling pathway. Further studies are needed to investigate what role other known neurotrophic factors may play in this process. Key Findings Capsaicin treatment stimulates corneal sensory nerves and depletes them of neurotransmitters, including Substance P. Capsaicin treatment causes nerve regression and diminished innervation in the cornea. Hyperstimulation of corneal nerves with capsaicin inhibits cornea‐lens regeneration in the frog Xenopus. Modulation of Substance P through its receptor NK‐1 does not affect cornea‐lens regeneration. Corneal nerves play a key role in supporting lens regeneration, but the identity of key neurotrophic factors remains unknown.