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

2020 ◽  
Vol 14 ◽  
Author(s):  
Adrian Guerrero-Moreno ◽  
Christophe Baudouin ◽  
Stéphane Melik Parsadaniantz ◽  
Annabelle Réaux-Le Goazigo
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Inflammatory Responses ◽  
The Body ◽  
Surgical Interventions ◽  
Sensory Abnormalities ◽  
Functional Changes ◽  
Neuroimmune Interactions ◽  
Corneal Nerves ◽  
Corneal Nerve

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.

scholarly journals In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3245
Author(s):  
Sung-Chul Hong ◽  
Jung-Heun Ha ◽  
Jennifer K. Lee ◽  
Sang Hoon Jung ◽  
Jin-Chul Kim
Keyword(s):  
Animal Model ◽  
Er Stress ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Inflammatory Responses ◽  
Dry Eye Syndrome ◽  
Inhibitory Effects ◽  
Food Material

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.

scholarly journals Analysis of Clinical Characteristics of Immune-Related Dry Eye

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hua Wang ◽  
Ping-Bao Wang ◽  
Ting Chen ◽  
Jing Zou ◽  
Ya-Jia Li ◽  
...  
Keyword(s):  
Dry Eye ◽  
Lupus Erythematosus ◽  
Ocular Surface ◽  
Clinical Characteristics ◽  
Nerve Fibers ◽  
Immune System Diseases ◽  
Corneal Nerve ◽  
The Difference ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Aim. To discuss the clinical characteristics of immune-related dry eye. Methods. Simple dry eye (SDE) group: we selected 224 patients of simple dry eye with no systemic lesions. Immune-related dry eye (IRDE) group: we selected 207 patients of dry eye complicated with immune system diseases, including 70 cases of Sjögren’s syndrome (SS), 72 cases of systemic lupus erythematosus (SLE), and 65 cases of rheumatoid arthritis (RA). The classification of all patients was performed. The difference between the two groups was compared, including age, gender, ocular surface fluorescein staining and inflammatory reaction, tear breakup time (TBUT), Shirmer I test, confocal microscopy scan, and dry eye grading. Results. Compared with the SDE group, the patients of IRDE group were younger (P<0.05). The female patients were significantly more than the male ones (P<0.05). Corneal staining counts and ocular surface inflammation were significantly increased (P<0.05). TBUT and Shirmer I test shortened significantly (P<0.05). Corneal nerve fibers were less, and the number of local lymphocyte was significant increased. The number of dry eye patients in the moderate or above IRDE group was significantly increased (P<0.05). Conclusions. The dry eye symptom and sign and ocular surface inflammation of IRDE were significantly more severe than those of the SDE.

scholarly journals Thrombospondin-1 Is Necessary for the Development and Repair of Corneal Nerves

2018 ◽  
Vol 19 (10) ◽  
pp. 3191 ◽  
Author(s):  
Yukako Tatematsu ◽  
Qalbi Khan ◽  
Tomas Blanco ◽  
Jeffrey Bair ◽  
Robin Hodges ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Sjögren’S Syndrome ◽  
Dry Eye ◽  
Ocular Surface ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Corneal Nerves ◽  
Thrombospondin 1 ◽  
Sjögren‘S Syndrome

Thrombospondin-1-deficient (TSP-1−/−) mice are used as an animal model of Sjögren’s Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sjögren’s Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1−/− and wild type (WT) mice. The structure and subtype of nerves were characterized by immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. Cytokine expression analysis was determined by Q-PCR and the number of monocytes was measured by immunohistochemistry. We found that only the pro-inflammatory cytokine MIP-2 increased in young corneas of TSP-1−/− compared to WT mice, but tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1−/− mouse corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P (SubP)-containing corneal nerves decreased in older, but not younger TSP-1−/− compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory nerves exhibit distinct structural deficiencies as disease progresses in TSP-1−/− mice, suggesting that: (1) TSP-1 is needed for the development or repair of these nerves and (2) impaired afferent corneal nerve structure and hence function may contribute to ocular surface dysfunction that develops as TSP-1−/− mice age.

scholarly journals Neurotrophic keratitis in autoimmune polyglandular syndrome type 1: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Po-Ying Wu ◽  
Huai-Wen Chang ◽  
Wei-Li Chen
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Hypogonadotropic Hypogonadism ◽  
Ocular Surface Disease ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Corneal Nerves ◽  
Neurotrophic Keratitis ◽  
Autoimmune Polyglandular Syndrome Type

Abstract Background Autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive disease. In patients with APS-1, the most frequently reported ocular manifestations are keratoconjunctivitis with dry eye and retinal degeneration. However, to our knowledge, no research studies have reported the relationship between APS-1 and neurotrophic keratitis (NK). Possible explanations such as limbus cell deficiency being the primary cause of APS-1 keratopathy are not applicable to our unusual case of the patient with APS-1 presenting as ocular surface disease with NK. Our case findings suggest a new explanation for the observed corneal pathology and a potential treatment for these patients. Case presentation A 27-year-old woman was referred to our hospital because of intermittent blurred vision and recalcitrant ocular surface problems in both eyes for many years. She has a history of autoimmune polyglandular syndrome type 1 (APS-1), which includes hypothyroidism, hypoparathyroidism, hypoadrenalism, and hypogonadotropic hypogonadism. In vivo confocal microscopy clearly demonstrated significant degeneration of the sub-basal nerve plexus and stromal nerve bundles in her corneas bilaterally. She was diagnosed with severe NK and ocular surface disease caused by dry eye. Treatment included the application of therapeutic soft contact lenses and punctual occlusion; however, both treatments had a limited effect. Conclusion Patients with APS-1 may have ocular surface disease and severe damage to corneal nerves. Regular follow-up and treatment focusing on the regeneration of corneal nerves is particularly important in these patients.

scholarly journals Evaluation of objective visual quality in dry eye disease and corneal nerve changes

2020 ◽  
Vol 40 (11) ◽  
pp. 2995-3004
Author(s):  
Jiahui Ma ◽  
Shanshan Wei ◽  
Xiaodan Jiang ◽  
Yilin Chou ◽  
Yuexin Wang ◽  
...  
Keyword(s):  
Dry Eye ◽  
Clinical Symptoms ◽  
Visual Quality ◽  
Strehl Ratio ◽  
Modulation Transfer ◽  
Ocular Surface Disease Index ◽  
Eyelid Margin ◽  
Cutoff Value ◽  
Corneal Nerves ◽  
Corneal Nerve

Abstract Purpose To explore objective visual quality in dry eye diseases (DED) and the correlation between corneal nerves and objective visual quality. Methods Ninety-eight eyes of 49 patients with DED were included. Each patient was evaluated with the ocular surface disease index (OSDI), eyelid margin signs and meibomian gland assessments; corneal staining; tear film breakup time (TBUT); tear meniscus height (TMH); in vivo confocal microscopic (IVCM); objective visual quality including the objective scatter index (OSI), mean objective scattering index (mOSI), modulation transfer function (MTF) cutoff value and Strehl ratio. Results A significant correlation was found between the OSDI and mOSI (r = 0.422, p = 0.005), MTF cutoff value (r = − 0.355, p = 0.020), and Strehl ratio (r = − 0.446, p = 0.003). The OSI was significantly correlated with TBUTf (r = − 0.213, p = 0.042). The mOSI, MTF cutoff value, Strehl ratio were correlated with eyelid margin signs and meibomian assessments. Additionally, there was a statistically significant correlation between corneal nerve length and the mOSI (r = − 0.239, p = 0.037), OSI (r = − 0.294, p = 0.028), MTF cutoff value(r = 0.282, p = 0.012), and Strehl ratio (r = 0.299, p = 0.008). Conclusions Our study explored that objective visual quality was correlated with clinical symptoms and signs in DED patients. Furthermore, for the first time, our study explored the relationship between corneal nerves and objective visual quality and discovered that longer and wider corneal nerves were associated with better objective visual quality, which suggested that nerve changes may be a factor that related to poor visual quality in DED patients.

scholarly journals A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeremy Chung Bo Chiang ◽  
David Goldstein ◽  
Terry Trinh ◽  
Kimberley Au ◽  
Susanna B. Park ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Peripheral Neurotoxicity ◽  
Patient Reported ◽  
Paclitaxel Group ◽  
Corneal Nerve ◽  
Paclitaxel Treatment

AbstractOcular surface dysfunction is common in patients receiving anti-cancer drug treatment. The effects of paclitaxel, a neurotoxic chemotherapeutic drug, on ocular surface discomfort associated with dry eye disease was investigated. Patients with cancer who had completed paclitaxel treatment between 3 and 24 months prior to assessment (n = 29) and age- and sex-matched healthy control subjects (n = 29) were recruited and assessed with the Ocular Surface Disease Index (OSDI) to measure ocular surface discomfort. In-vivo corneal confocal microscopy was used to evaluate corneal nerve parameters in the right eye. Peripheral neurotoxicity was assessed using patient-reported outcomes and clinical grading scales. The paclitaxel group had significantly worse OSDI total scores compared with controls (Median, Md = 19.3 and Md = 0, p = 0.007, respectively). Corneal nerve fiber and inferior whorl lengths were reduced in the paclitaxel group compared with controls (14.2 ± 4.0 and 14.4 ± 4.0 mm/mm2 vs. 16.4 ± 4.0 and 16.9 ± 4.9 mm/mm2, respectively, p = 0.04). When analyzed by presence of peripheral neuropathy, paclitaxel-treated patients with neuropathy showed worse OSDI total scores compared to those without peripheral neuropathy post-treatment (p = 0.001) and healthy controls (p < 0.001). More severe ocular discomfort and worse visual function was associated with greater peripheral neurotoxicity symptoms (r = 0.60, p = 0.001) and neuropathy severity (r = 0.49, p = 0.008), respectively. Patients who have been treated with paclitaxel have a higher risk of ocular surface discomfort associated with dry eye disease, particularly those with peripheral neuropathy. Future longitudinal studies should investigate the clinical impact of corneal nerve reduction in dry eye disease.

scholarly journals The Role of Neuropeptides in Pathogenesis of Dry Dye

2021 ◽  
Vol 10 (18) ◽  
pp. 4248
Author(s):  
Daniel Duck-Jin Hwang ◽  
Seok-Jae Lee ◽  
Jeong-Hun Kim ◽  
Sang-Mok Lee
Keyword(s):  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Future Research ◽  
Immune Systems ◽  
Pathogenic Mechanisms ◽  
Corneal Nerves ◽  
Ocular Surface Diseases ◽  
Corneal Nerve

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.

scholarly journals Evaluation of the condition of the eye surface in patients with burdened general somatic history. Early diagnosis, treatment and prevention methods

2020 ◽  
pp. 56-62
Author(s):  
I.E. Shvailikova ◽  
◽  
E.I. Belikova ◽  
Keyword(s):  
Dry Eye ◽  
Postoperative Period ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Additional Treatment ◽  
Dry Eye Syndrome ◽  
Comprehensive Treatment ◽  
Inflammatory Reactions ◽  
Surgical Interventions ◽  
Somatic Status

Introduction. Modern computerisation, frequent use of contact correction, surgical interventions on the visual organ and long-term drug installations often lead to the formation and further progression of dry eye syndrome (DES) with subsequent increased sensitivity and inflammatory symptoms on the conjunctiva and cornea. Purpose. Evaluation of the condition of the eye surface in patients with a burdened general somatic history. Development of measures for prevention, diagnosis and comprehensive treatment of this condition. Material and methods. A retrospective analysis of disease histories and medical records of 108 patients (108 eyes) with phacoemulsification of uncomplicated cataract with IOL implantation was carried out. Patients were divided into three main groups based on the presence of burdening factors of somatic status and the course of the postoperative period: I group included patients with unburdened somatic status and no complications during the course of the postoperative period; II group included patients with burdened general somatic history with complications during the course of the postoperative period; 3rd group included patients with burdened general somatic history with complications during the course of the postoperative period. 3rd group of patients used a special scheme to prevent and treat inflammatory reactions from the eye surface. Results. 1st group patients were less likely to complain and had no clinical manifestations of conjunctival and corneal inflammatory responses. Accordingly, this group of patients did not require additional treatment, which is indicative of the low incidence of complications in this category of patients. II group patients who had been identified as predisposing factors for conjunctival and corneal inflammatory reactions and did not receive additional treatment were more likely to experience complaints and the frequency of clinical manifestations was 20% higher than III group patients. Patients in III group required additional treatment in the postoperative period. Conclusion. Prolonged prescription of high doses of drugs of different groups with different preservative and auxiliary substances content in patients after surgical intervention in some cases leads to damage to the conjunctival and corneal epithelium, which in turn causes an aggravation of symptoms of SSG with the development of inflammatory reaction of the conjunctiva and cornea. The application of preventive measures before and after the surgery leads to a significant reduction in the objective manifestations of the eye surface complications and, as a result, a reduction in the number of complaints from patients about discomfort in the postoperative period. Key words: ocular surface, dry eye syndrome, cataract, allergies, tear film stability.

scholarly journals Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

2018 ◽  
Author(s):  
Deborah M. Hegarty ◽  
Sam M. Hermes ◽  
Michael M. Morgan ◽  
Sue A. Aicher
Keyword(s):  
Dry Eye ◽  
Temporal Dynamics ◽  
Nerve Endings ◽  
Male Rats ◽  
Spontaneous Pain ◽  
Corneal Abrasion ◽  
Corneal Nerves ◽  
Eye Symptoms ◽  
Corneal Nerve ◽  
Dry Eye Symptoms

AbstractCorneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms.

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