Neuroimmune crosstalk in the cornea: The role of immune cells in corneal nerve maintenance during homeostasis and inflammation

Wu, Mengliang; Hill, Lisa J; Downie, Laura E; Chinnery, Holly R.

doi:10.1016/j.preteyeres.2022.101105

Cited by 29 publications

(36 citation statements)

References 381 publications

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“…Under normal conditions, the cornea is endowed with a heterogeneous resident population of antigen-presenting cells, including dendritic cells and macrophages (101)(102)(103). Several lines of evidence revealed that specific deletion of dendritic cells or macrophages results in a delayed corneal wound healing in healthy or DM corneas (74,(104)(105)(106).…”

Section: Chronic Inflammationmentioning

confidence: 99%

Mechanistic investigations of diabetic ocular surface diseases

et al. 2022

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With the global prevalence of diabetes mellitus over recent decades, more patients suffered from various diabetic complications, including diabetic ocular surface diseases that may seriously affect the quality of life and even vision sight. The major diabetic ocular surface diseases include diabetic keratopathy and dry eye. Diabetic keratopathy is characterized with the delayed corneal epithelial wound healing, reduced corneal nerve density, decreased corneal sensation and feeling of burning or dryness. Diabetic dry eye is manifested as the reduction of tear secretion accompanied with the ocular discomfort. The early clinical symptoms include dry eye and corneal nerve degeneration, suggesting the early diagnosis should be focused on the examination of confocal microscopy and dry eye symptoms. The pathogenesis of diabetic keratopathy involves the accumulation of advanced glycation end-products, impaired neurotrophic innervations and limbal stem cell function, and dysregulated growth factor signaling, and inflammation alterations. Diabetic dry eye may be associated with the abnormal mitochondrial metabolism of lacrimal gland caused by the overactivation of sympathetic nervous system. Considering the important roles of the dense innervations in the homeostatic maintenance of cornea and lacrimal gland, further studies on the neuroepithelial and neuroimmune interactions will reveal the predominant pathogenic mechanisms and develop the targeting intervention strategies of diabetic ocular surface complications.

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Section: Chronic Inflammationmentioning

confidence: 99%

Mechanistic investigations of diabetic ocular surface diseases

et al. 2022

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“…Sensory denervation by trigeminal axotomy leads to decreased tear secretion, a loss of immune privilege, and an enhanced cDC migration and motility [ 64 ]. While corneal cDCs display minimal motility during the steady state [ 18 , 65 ], following sensory denervation, corneal cDCs greatly increase motility in a random walk fashion [ 21 ]. Sensory denervation also upregulates vascular adhesion molecules, thereby promoting leukocyte adhesion, rolling, and sticking and ultimately leading to an influx of bone marrow-derived cells into the cornea [ 20 , 21 , 66 ].…”

Section: Corneal Innervationmentioning

confidence: 99%

“…While corneal cDCs display minimal motility during the steady state [ 18 , 65 ], following sensory denervation, corneal cDCs greatly increase motility in a random walk fashion [ 21 ]. Sensory denervation also upregulates vascular adhesion molecules, thereby promoting leukocyte adhesion, rolling, and sticking and ultimately leading to an influx of bone marrow-derived cells into the cornea [ 20 , 21 , 66 ]. Recent studies have shown that these mechanisms of neuroimmune crosstalk in the cornea could largely be via interactions between neuropeptides expressed by corneal nerves and their receptors in RCLs [ 19 , 21 , 67 , 68 , 69 , 70 ].…”

Section: Corneal Innervationmentioning

confidence: 99%

“…Sensory denervation also upregulates vascular adhesion molecules, thereby promoting leukocyte adhesion, rolling, and sticking and ultimately leading to an influx of bone marrow-derived cells into the cornea [20,21,66]. Recent studies have shown that these mechanisms of neuroimmune crosstalk in the cornea could largely be via interactions between neuropeptides expressed by corneal nerves and their receptors in RCLs [19,21,[67][68][69][70].…”

Section: Corneal Innervationmentioning

confidence: 99%

“…Several studies have shown a significant structural association and a functional interdependence between immune cells and sensory nerves in the cornea [ 9 , 15 , 16 , 17 , 18 , 19 , 20 ]. Since both the corneal nerves and RCLs share the expression of neuropeptides and their respective receptors, crosstalk may occur via the neuropeptide–receptor interaction [ 17 , 21 , 22 , 23 ]. Thus, understanding the immunomodulatory role of corneal neuropeptides could lead to the discovery of new therapeutic targets for the maintenance and restoration of corneal transparency in different pathological conditions or after surgical procedures such as corneal transplantation and refractive surgeries.…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory Role of Neuropeptides in the Cornea

2022

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The transparency of the cornea along with its dense sensory innervation and resident leukocyte populations make it an ideal tissue to study interactions between the nervous and immune systems. The cornea is the most densely innervated tissue of the body and possesses both immune and vascular privilege, in part due to its unique repertoire of resident immune cells. Corneal nerves produce various neuropeptides that have a wide range of functions on immune cells. As research in this area expands, further insights are made into the role of neuropeptides and their immunomodulatory functions in the healthy and diseased cornea. Much remains to be known regarding the details of neuropeptide signaling and how it contributes to pathophysiology, which is likely due to complex interactions among neuropeptides, receptor isoform-specific signaling events, and the inflammatory microenvironment in disease. However, progress in this area has led to an increase in studies that have begun modulating neuropeptide activity for the treatment of corneal diseases with promising results, necessitating the need for a comprehensive review of the literature. This review focuses on the role of neuropeptides in maintaining the homeostasis of the ocular surface, alterations in disease settings, and the possible therapeutic potential of targeting these systems.

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