Role of corneal nerves in ocular surface homeostasis and disease

Abstract

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset

“…[24][25][26] It remains to be established whether these changes represent a core pathophysiological mechanism of DED or an epiphenomenon associated with ocular surface inflammation. 28 Corneal DCs and sensory nerves are both structurally and functionally interdependent in mice. 55,56 Remarkably, in our model THO also increased conjunctival DC number and activation and reduced corneal nerve density.…”

“…[24][25][26] Besides, the cornea is densely innervated, and regulatory neuroimmune crosstalk is crucial for ocular surface homeostasis. [27][28][29] Corneal intraepithelial nerves terminate as free nerve endings interspersed between the apical squamous epithelial cells, almost in direct contact with the tear film. 30 In a DED model, desiccating stress rapidly induces a break in the apical corneal epithelial barrier, 31 along with structural and functional alterations in corneal intraepithelial nerves.…”

Erkrankungen der Lider und Augenoberfläche

“…Eine weitere wichtige Komponente für eine gesunde Augenoberfläche sind intakte Hornhautnerven [5]. Sie schützen die Augenoberfläche, indem sie für einen reflektorischen Lidschluss und gesteigerte Tränensekretion sorgen.…”

“…Störungen der cornealen Neurosensorik können zu reduzierter Hornhautsensibilität, reduzierter Tränenproduktion, Schmerzen und persistierenden Augenoberflächendefekten, wie z.B. bei der neurotrophen Keratopathie, führen [5,6]. Eine Amnionmembrantransplantation ist eine wertvolle Therapieoption bei persistierenden Augenoberflächendefekten, da sie antiinflammatorisch wirkt und Faktoren enthält, die die Wundheilung anregen [7].…”

Sensory neurons directly promote angiogenesis in response to inflammation via substance P signaling

“…The cornea is innervated by the ophthalmic branch of the trigeminal nerve (cranial nerve V1). Nerve fibers originate from the trigeminal ganglion, enter the cornea from the limbus, transverse in stroma, and then form subbasal nerve plexus that supplies the overlying epithelium . In addition to their sensory function, corneal nerves modulate the blink reflex, tear production, and stem cell niche maintenance .…”