Neurotrophic keratitis as a peripheral sensory neurodegenerative disease

Abstract

AbstractMaintenance of the ocular surface critically depends on the nocifensive responses elicited by the proper functioning of corneal sensory innervation. Damage of any type caused to the trigeminal ganglion or its ophthalmic branch is associated to the development of chronic trophic disturbances of the corneal epithelium homeostasis, which may progress to corneal perforation and vision loss. Since the first observations by Magendie as early as in 1824, many efforts have been dedicated to identifying the molecular mechanisms underlying the trophic effects exerted by sensory neurons on corneal tissue.Many molecules derived or released by sensory nerves have been involved in corneal epithelial wound healing, either in vivo or in vitro. Neuropeptides released from the intraepithelial free nerve endings of corneal polymodal nociceptors have been claimed as potential candidate molecules to explain the trophic effects of sensory neurons on the corneal epithelium. However, their precise role in basal maintenance of the corneal epithelium or during corneal wound healing is far from being clearly understood. Consequently, neurotrophic keratitis is still considered as an orphan disease, and its association to the trigeminal sensory neuron degeneration is the rationale for assaying neuroregenerative therapies, such as neurotrophin eyedrops or neurotization, as potential treatments.(Supported by grants SAF‐2017‐83674‐C2‐1‐R and 2‐R from Agencia Estatal de Investigación, Spain, and ERDF, EU, and PROMETEO/2018/114 from Generalitat Valenciana, and in part by Horizon 2020 G.A. No 667400, European Commission)