The two-faced effects of nerves and neuropeptides in corneal diseases

Vitar, Romina Mayra Lasagni; Rama, Paolo; Ferrari, Giulio

doi:10.1016/j.preteyeres.2021.100974

Cited by 36 publications

(37 citation statements)

References 222 publications

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“…Neuropeptides released by afferent nerve terminals function as both neurotransmitters and neuromodulators that lead to pain sensation [80][81][82] or neurogenic inflammatory responses [3,5,6]. The representative neuropeptides known to modulate immune reactions in response to external stimuli (mechanical, cold, and chemical stimuli; inflammatory mediators; damage-associated molecular patterns; and pathogen-associated molecular patterns) include SP, CGRP, VIP, and NPY [82][83][84][85][86][87].…”

Section: Representative Neuropeptides and Their Receptorsmentioning

confidence: 99%

“…In addition to this candidate, clinical trials for possible therapeutic agents can be performed based on the concepts suggested in this review in the future. However, considering that neuropeptides have effects similar to a double-edged sword [5], the balance between their positive effects, such as suppressing the pathogenic mechanism of DED, and their negative effects, such as suppression of wound healing and innate immunity against infection, should be thoroughly evaluated before initiating clinical trials.…”

Section: Future Directionsmentioning

confidence: 99%

“…Damage or stimulation to sensory nerve endings caused by pathogens or mechanical damage results in the secretion of neuropeptides, which play important roles in triggering and regulating inflammatory responses, and this series of processes is called neurogenic inflammation [2,3]. Neurogenic inflammation is caused by small sensory nerves with relatively slow conduction speeds (unmyelinated C-fibers and finely myelinated Afibers, Aδ fibers), which are densely innervated in the ocular surface [2,5]. Neuropeptides, including small-molecule peptides secreted by nerve endings represented by substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY), are known as important players in neuroimmune crosstalk [2,6].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Neuropeptides in Pathogenesis of Dry Eye

Hwang

Lee

Kim

et al. 2021

JCM

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Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the pathogenesis of dry eye disease, as suggested by the well-known role between the nervous and immune systems, and several recently published studies have elucidated the previously unknown pathogenic mechanisms involved in the role of the neuropeptides secreted from the corneal nerves in dry eye disease. Here, we reviewed the emerging concept of neurogenic inflammation as one of the pathogenic mechanisms of dry eye disease, the recent results of related studies, and the direction of future research.

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Section: Representative Neuropeptides and Their Receptorsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of Neuropeptides in Pathogenesis of Dry Eye

Hwang

Lee

Kim

et al. 2021

JCM

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“…From a pathophysiological standpoint, corneal nerves present a two-faced role in corneal homeostasis. On the one hand, they contribute to the maintenance of corneal integrity by secreting trophic neuropeptides (such as substance P (SP), calcitonin-gene related peptide (CGRP), pituitary adenylate cyclase-activation polypeptide (PACAP), and vasoactive intestinal peptide (VIP) [ 28 ]), promoting proper tear secretion and blink reflex [ 29 ]. On the other hand, acute and/or chronic dysfunction of corneal nerves can initiate neurogenic inflammation via CGRP/SP-mediated signaling and may eventually lead to corneal opacification and vision impairment.…”

Section: A Primer On Corneal Anatomy and Corneal Wound Healingmentioning

confidence: 99%

Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing

Zhang

Mélik-Parsadaniantz

Baudouin

et al. 2022

IJMS

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The cornea, an anterior ocular tissue that notably serves to protect the eye from external insults and refract light, requires constant epithelium renewal and efficient healing following injury to maintain ocular homeostasis. Although several key cell populations and molecular pathways implicated in corneal wound healing have already been thoroughly investigated, insufficient/impaired or excessive corneal wound healing remains a major clinical issue in ophthalmology, and new avenues of research are still needed to further improve corneal wound healing. Because of its implication in numerous cellular/tissular homeostatic processes and oxidative stress, there is growing evidence of the role of Hedgehog signaling pathway in physiological and pathological corneal wound healing. Reviewing current scientific evidence, Hedgehog signaling and its effectors participate in corneal wound healing mainly at the level of the corneal and limbal epithelium, where Sonic Hedgehog-mediated signaling promotes limbal stem cell proliferation and corneal epithelial cell proliferation and migration following corneal injury. Hedgehog signaling could also participate in corneal epithelial barrier homeostasis and in pathological corneal healing such as corneal injury-related neovascularization. By gaining a better understanding of the role of this double-edged sword in physiological and pathological corneal wound healing, fascinating new research avenues and therapeutic strategies will undoubtedly emerge.

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“…More than 50 types of neuropeptides have been isolated and their structures elucidated ( Table 2 ) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. These are amino acid complexes range in size from two to several dozen, some of which are present in the brain and perform neurochemical, neurophysiological, neuropharmacological, and behavioral functions.…”

Section: Neuropeptidesmentioning

confidence: 99%

Neuropeptides Involved in Facial Nerve Regeneration

Kim

Kang

et al. 2021

Biomedicines

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Neuropeptides and neurotransmitters act as intermediaries to transmit impulses from one neuron to another via a synapse. These neuropeptides are also related to nerve degeneration and regeneration during nerve damage. Although there are various neuropeptides, three are associated with neural regeneration in facial nerve damage: calcitonin gene-related peptide (CGRP), galanin, and pituitary adenylyl cyclase-activating peptide (PACAP). Alpha CGRP in facial motoneurons is a signaling factor involved in neuroglial and neuromuscular interactions during regeneration. Thus, it may be a marker for facial nerve regeneration. Galanin is a marker of injured axons rather than nerve regeneration. PACAP has various effects on nerve regeneration by regulating the surrounding cells and providing neurotrophic factors. Thus, it may also be used as a marker for facial nerve regeneration. However, the precise roles of these substances in nerve generation are not yet fully understood. Animal studies have demonstrated that they may act as neuromodulators to promote neurotrophic factors involved in nerve regeneration as they appear early, before changes in the injured cells and their environment. Therefore, they may be markers of nerve regeneration.

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The two-faced effects of nerves and neuropeptides in corneal diseases

Cited by 36 publications

References 222 publications

The Role of Neuropeptides in Pathogenesis of Dry Eye

The Role of Neuropeptides in Pathogenesis of Dry Eye

Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing

Neuropeptides Involved in Facial Nerve Regeneration

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