Expression of Cholecystokinin, Gastrin, and Their Receptors in the Mouse Cornea

Gonzalez-Coto, Ana F.; Alonso-Ron, Carlos; Alcalde, Ignacio; Gallar, Juana; Meana, Álvaro; Merayo‐Lloves, Jesús; Belmonte, Carlos

doi:10.1167/iovs.13-12068

Cited by 17 publications

(11 citation statements)

References 56 publications

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“…However, the roles of CGRP and substance P in the neuro-immune cross-talk at the ocular surface in DED are yet to be elucidated. Other neuropeptides (cholecystokinin, gastrin) have been also detected in the cornea and TG neurons [159]. However, their functional role remains enigmatic.…”

Section: Neurobiological Features In Normal/non Dry Eye Diseasementioning

confidence: 99%

TFOS DEWS II pain and sensation report

et al. 2017

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Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.

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Section: Neurobiological Features In Normal/non Dry Eye Diseasementioning

confidence: 99%

TFOS DEWS II pain and sensation report

et al. 2017

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“…8 Murine, 24 primate, 25 and human studies suggest that these sympathetic nerves release neuropeptides that may be involved in corneal neurogenic inflammation and remodelling following corneal injury. 24,25 …”

Section: Embryology Of Corneal Nervesmentioning

confidence: 99%

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

2017

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In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

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“…All SP + terminals are CGRP + in mice (Ivanusic et al, 2013). Other mediators are also found, such as neurokinin A, serotonin, somatostatin, as well as cholecystokinin or gastrin (Gonzalez-Coto et al, 2014). In humans, to date, only substance P and CGRP have been clearly identified in corneal fibers.…”

Section: Functional Classification Of Corneal Fibersmentioning

confidence: 99%

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

Guerrero-Moreno

Baudouin

Mélik-Parsadaniantz

et al. 2020

Front. Cell. Neurosci.

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The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.

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Expression of Cholecystokinin, Gastrin, and Their Receptors in the Mouse Cornea

Cited by 17 publications

References 56 publications

TFOS DEWS II pain and sensation report

TFOS DEWS II pain and sensation report

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

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