The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease

Tan, Xuhua; Chen, Yihe; Foulsham, William; Amouzegar, Afsaneh; Inomata, Takenori; Liu, Yizhi; Chauhan, Sunil; Dana, Reza

doi:10.1016/j.jtos.2018.07.005

Cited by 30 publications

(20 citation statements)

References 45 publications

(53 reference statements)

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“… 87 In a mouse model of DED, it has been observed that TSP-1 levels were increased in the cornea. 88 Moreover, recombinant TSP-1, administered topically, decreased expression of proinflammatory cytokines (IL-1β, IL-6, IL-23, IL-17A) in the conjunctiva and in the cornea, and ameliorated disease severity. Moreover, topical TSP-1 significantly suppressed corneal dendritic cell maturation.…”

Section: Novel Emerging Therapies For Ded Acting Through Other Mechanmentioning

confidence: 99%

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Experimental Pharmacotherapy for Dry Eye Disease: A Review

Baiula¹,

Spampinato²

2021

JEP

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Dry eye disease (DED) is a complex multifactorial disease showing heterogenous symptoms, including dryness, photophobia, ocular discomfort, irritation and burning but also pain. These symptoms can affect visual function leading to restrictions in daily life activities and reduction in work productivity with a consequently high impact on quality of life. Several pathological mechanisms contribute to the disease: evaporative water loss leads to impairment and loss of tear homeostasis inducing either directly or indirectly to inflammation, in a self-perpetuating vicious cycle. Dysregulated ocular immune responses result in ocular surface damage, which further contributes to DED pathogenesis. Currently, DED treatment is based on a flexible stepwise approach to identify the most beneficial intervention. Although most of the available treatments may control to a certain extent some signs and symptoms of DED, they show significant limitations and do not completely address the needs of patients suffering from DED. This review provides an overview of the emerging experimental therapies for DED. Several promising therapeutic strategies are under development with the aim of dampening inflammation and restoring the homeostasis of the ocular surface microenvironment. Results from early phase clinical trials, testing the effects of EnaC blockers, TRPM8 agonist or mesenchymal stem cells in DED patients, are especially awaited to demonstrate their therapeutic value for the treatment of DED. Moreover, the most advanced experimental strategies in the pipeline for DED, tivanisiran, IL-1R antagonist EBI-005 and SkQ1, are being tested in Phase III clinical trials, still ongoing. Nevertheless, although promising results, further studies are still needed to confirm efficacy and safety of the new emerging therapies for DED.

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Section: Novel Emerging Therapies For Ded Acting Through Other Mechanmentioning

confidence: 99%

“…Moreover, topical TSP-1 significantly suppressed corneal dendritic cell maturation. 88 Within this frame, TSP-1 could represent an interesting innovative approach for DED treatment. Nevertheless, to date, no clinical trials are ongoing to evaluate the effects of TSP-1 for DED treatment.…”

Section: Novel Emerging Therapies For Ded Acting Through Other Mechanmentioning

confidence: 99%

Experimental Pharmacotherapy for Dry Eye Disease: A Review

Baiula¹,

Spampinato²

2021

JEP

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“…Thrombospondin-1 (TSP-1) activates TGF-β, which plays an immunomodulatory role at the ocular surface [129]. Tan et al [130] found that TSP-1 levels are upregulated in the corneas of mice with DED, and interestingly, expression of MHC II by bone-marrow-derived DCs (BMDCs) decreased significantly following co-culture with epithelial cells from DED mice. Further addition of recombinant (r)TSP-1 potentiated the suppressive effect of epithelial cells on BMDC maturation, whereas TSP-1 blockade ameliorated this effect.…”

Section: Emerging Ded-treatment Strategiesmentioning

confidence: 99%

Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy

Heidari

Noorizadeh

et al. 2019

JCM

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Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have seen new developments in clinical assessment approaches and treatment strategies in the recent past. Here, we review the emerging frontiers in the pathobiology and clinical management of DED.

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“…For example, following corneal injury, TSP-1 expression is observed in the stroma (where it is usually undetectable) underlying the wounded epithelium at 24 hours post-injury, and reaches peak expression after approximately one week [59]. In experimental DED, exposure to a desiccating environment increases corneal epithelial expression of TSP-1 [62]. Interestingly, Soriano-Romani and colleagues have reported that the expression of TSP-1 by conjunctival fibroblasts is decreased after in vitro stimulation with IL-1β in serum-free culture conditions, although this effect was not observed in serum-supplemented cultures [63].…”

Section: Distribution Of Tsp-1 In Ocular Surface Tissuesmentioning

confidence: 99%

Thrombospondin-1 in ocular surface health and disease

et al. 2019

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Thrombospondin 1 (TSP-1) is an extracellular matrix protein that interacts with a wide array of ligands including cell receptors, growth factors, cytokines and proteases to regulate various physiological and pathological processes. Constitutively expressed by certain ocular surface tissues (e.g. corneal and conjunctival epithelium), TSP-1 expression is modulated during ocular surface inflammation. TSP-1 is an important activator of latent TGF-β, serving to promote the immunomodulatory and wound healing functions of TGF-β. Mounting research has deepened our understanding of how TSP-1 expression (and lack thereof) contributes to ocular surface homeostasis and disease. Here, we review current knowledge of the function of TSP-1 in dry eye disease, ocular allergy, angiogenesis/lymphangiogenesis, corneal transplantation, corneal wound healing and infectious keratitis.

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The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease

Abstract: Our study elucidates the function of epithelium-derived TSP-1 in inhibiting DC maturation and shows its translational potential to limit corneal epitheliopathy in DED.

Cited by 30 publications

References 45 publications

Experimental Pharmacotherapy for Dry Eye Disease: A Review

Experimental Pharmacotherapy for Dry Eye Disease: A Review

Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy

Thrombospondin-1 in ocular surface health and disease

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