scholarly journals Changes in Murine Subbasal Corneal Nerves After Scopolamine-Induced Dry Eye Stress Exposure

2019 ◽  
Vol 60 (2) ◽  
pp. 615 ◽  
Author(s):  
Cem Simsek ◽  
Takashi Kojima ◽  
Taeko Nagata ◽  
Murat Dogru ◽  
Kazuo Tsubota
Keyword(s):  
Dry Eye ◽  
Stress Exposure ◽  
Corneal Nerves

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 Omega-3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study

2017 ◽  
Vol 37 (4) ◽  
pp. 473-481 ◽  
Author(s):  
Holly R. Chinnery ◽  
Cecilia Naranjo Golborne ◽  
Laura E. Downie
Keyword(s):  
Pilot Study ◽  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Omega 3 ◽  
Corneal Nerves

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 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 The Effects of Rebamipide 2% Ophthalmic Solution Application on Murine Subbasal Corneal Nerves After Environmental Dry Eye Stress

2019 ◽  
Vol 20 (16) ◽  
pp. 4031
Author(s):  
Cem Simsek ◽  
Takashi Kojima ◽  
Shigeru Nakamura ◽  
Murat Dogru ◽  
Kazuo Tsubota
Keyword(s):  
Dry Eye ◽  
Ophthalmic Solution ◽  
Inflammatory Cells ◽  
Office Workers ◽  
Therapeutic Effects ◽  
Fiber Density ◽  
Neuroprotective Effects ◽  
Staining Score ◽  
Corneal Nerves

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.

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 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.

scholarly journals Prominent corneal nerves, conjunctival neuromas, and dry eye in a patient without MEN2B

2019 ◽  
Vol 54 (6) ◽  
pp. e313-e317
Author(s):  
Kaevalin Lekhanont ◽  
Vachira Sontichai ◽  
Pattaramon Bunnapradist
Keyword(s):  
Dry Eye ◽  
Corneal Nerves
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