Fanny Joubert1, Maria Del Carmen Acosta2, Juana Gallar2, Darine Fakih1,3, José-Alain Sahel1,4, Christophe Baudouin1,4,5, Laurence Bodineau6, Stéphane Mélik Parsadaniantz1, Annabelle Réaux-Le Goazigo1. 1. INSERM, CNRS, Institut de la Vision, Sorbonne Université, Paris, France. 2. Instituto de Neurosciencas, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Alicante, Spain. 3. Laboratoires Théa, Clermont-Ferrand, France. 4. INSERM-DGOS CIC 1423, CHNO des Quinze-Vingts, DHU Sight Restore, Paris, France. 5. University Versailles Saint Quentin en Yvelines, Versailles, France. 6. INSERM, Sorbonne Université, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France.
Abstract
BACKGROUND: Ocular surface diseases are among the most frequent ocular pathologies. Ocular pain following corneal injury is frequently observed in clinic. Corneal sensory innervation is supplied by ciliary nerves derived from ophthalmic division of the trigeminal ganglion. METHODS & RESULTS: Extracellular activity of the mouse ciliary nerve was first used to investigate the corneal responsiveness to chemical, mechanical and thermal stimulations in order to specifically study the responses of polymodal nociceptors, mechano-nociceptors and cold thermoreceptor in a control cornea. Then, in two models of corneal injury (repeated instillations of 0.02% benzalkonium chloride and corneal scraping), we first measured the corneal sensitivity to chemical (eye-wiping test) and mechanical (von Frey filaments) stimulation. Thereafter, we evaluated whether these corneal injuries modified the spontaneous and chemical stimulation-evoked activity of the ciliary nerve. Both models of injury induced a significant corneal chemical hypersensitivity correlated with an increase of the spontaneous activity of the ciliary nerve and a faster response of the ciliary nerve after a chemical stimulation. CONCLUSIONS: Overall, this study provides new insights into the functional aspects of corneal nerve fibre activity in mice after corneal injury. The increase in ciliary nerve activity may thus contribute to the development of ocular pain after corneal damage. SIGNIFICANCE: This study highlights the parallel increase in ciliary nerve activity and corneal sensitivity after corneal injury in mice. The strategy of combining ex vivo electrophysiological recordings of the ciliary nerve in mice and corneal sensitivity measurements therefore helps to uncover the functional aspects of corneal pain.
BACKGROUND: Ocular surface diseases are among the most frequent ocular pathologies. Ocular pain following corneal injury is frequently observed in clinic. Corneal sensory innervation is supplied by ciliary nerves derived from ophthalmic division of the trigeminal ganglion. METHODS & RESULTS: Extracellular activity of the mouse ciliary nerve was first used to investigate the corneal responsiveness to chemical, mechanical and thermal stimulations in order to specifically study the responses of polymodal nociceptors, mechano-nociceptors and cold thermoreceptor in a control cornea. Then, in two models of corneal injury (repeated instillations of 0.02% benzalkonium chloride and corneal scraping), we first measured the corneal sensitivity to chemical (eye-wiping test) and mechanical (von Frey filaments) stimulation. Thereafter, we evaluated whether these corneal injuries modified the spontaneous and chemical stimulation-evoked activity of the ciliary nerve. Both models of injury induced a significant corneal chemical hypersensitivity correlated with an increase of the spontaneous activity of the ciliary nerve and a faster response of the ciliary nerve after a chemical stimulation. CONCLUSIONS: Overall, this study provides new insights into the functional aspects of corneal nerve fibre activity in mice after corneal injury. The increase in ciliary nerve activity may thus contribute to the development of ocular pain after corneal damage. SIGNIFICANCE: This study highlights the parallel increase in ciliary nerve activity and corneal sensitivity after corneal injury in mice. The strategy of combining ex vivo electrophysiological recordings of the ciliary nerve in mice and corneal sensitivity measurements therefore helps to uncover the functional aspects of corneal pain.
Authors: Emilie Sophie van der Valk Bouman; Heather Pump; David Borsook; Boris Severinsky; Robert Pl Wisse; Hajirah N Saeed; Eric A Moulton Journal: BMJ Open Ophthalmol Date: 2021-11-29