Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves' ophthalmopathy

Dik, Willem A.; Virakul, Sita; Steensel, Leendert van

doi:10.1016/j.exer.2015.02.007

Cited by 121 publications

(134 citation statements)

References 98 publications

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“…It is characterized by extensive inflammation, expansion, remodeling and fibrosis of the soft tissues surrounding the eyes, resulting in enlargement of the extraocular muscles and accumulation of retrobulbar fat and connective tissue (Bahn, 2010). Due to the rigidity of the bony orbit, this increased orbital tissue volume displaces the globe forward resulting in clinical signs of proptosis, swollen eyelids, keratitis, conjunctivitis and optic neuropathy from optic nerve compression (Dik et al, 2016). …”

Section: Orbital Fibrosis In Graves’ Ophthalmopathymentioning

confidence: 99%

“…Orbital fibroblasts have been implicated as the primary target cells of the autoimmune process in GO (Dik et al, 2016). Once activated, orbital fibroblasts fulfil their key roles in orbital inflammation and tissue remodeling in GO by increasing their proliferative activity, producing inflammatory cytokines and differentiating into adipocytes or myofibroblasts (Dik et al, 2016).…”

Section: Orbital Fibrosis In Graves’ Ophthalmopathymentioning

confidence: 99%

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Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

Shu

Lovicu

2017

Progress in Retinal and Eye Research

273

239

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Wound healing is one of the most complex biological processes to occur in life. Repair of tissue following injury involves dynamic interactions between multiple cell types, growth factors, inflammatory mediators and components of the extracellular matrix (ECM). Aberrant and uncontrolled wound healing leads to a non-functional mass of fibrotic tissue. In the eye, fibrotic disease disrupts the normally transparent ocular tissues resulting in irreversible loss of vision. A common feature in fibrotic eye disease is the transdifferentiation of cells into myofibroblasts that can occur through a process known as epithelial-mesenchymal transition (EMT). Myofibroblasts rapidly produce excessive amounts of ECM and exert tractional forces across the ECM, resulting in the distortion of tissue architecture. Transforming growth factor-beta (TGFβ) plays a major role in myofibroblast transdifferentiation and has been implicated in numerous fibrotic eye diseases including corneal opacification, pterygium, anterior subcapsular cataract, posterior capsular opacification, proliferative vitreoretinopathy, fibrovascular membrane formation associated with proliferative diabetic retinopathy, submacular fibrosis, glaucoma and orbital fibrosis. This review serves to introduce the pathological functions of the myofibroblast in fibrotic eye disease. We also highlight recent developments in elucidating the multiple signaling pathways involved in fibrogenesis that may be exploited in the development of novel anti-fibrotic therapies to reduce ocular morbidity due to scarring.

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Section: Orbital Fibrosis In Graves’ Ophthalmopathymentioning

confidence: 99%

Section: Orbital Fibrosis In Graves’ Ophthalmopathymentioning

confidence: 99%

Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

Shu

Lovicu

2017

Progress in Retinal and Eye Research

273

239

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“…Orbital fibroblasts from healthy individuals appear to differ from those with TAO [11–13]. They represent a heterogeneous population of cells with divergent capacities for terminal differentiation and gene expression.…”

Section: Pathogenesismentioning

confidence: 99%

Update on thyroid-associated Ophthalmopathy with a special emphasis on the ocular surface

Novaes

Grisolia

Smith

2016

Clin Diabetes Endocrinol

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Thyroid-associated ophthalmopathy (TAO) is a condition associated with a wide spectrum of ocular changes, usually in the context of the autoimmune syndrome, Graves’ disease. In this topical review, we attempted to provide a roadmap of the recent advances in current understanding the pathogenesis of TAO, important aspects of its clinical presentation, its impact on the ocular surface, describe the tissue abnormalities frequently encountered, and describe how TAO is managed today. We also briefly review how increased understanding of the disease should culminate in improved therapies for patients with this vexing condition.

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“…Deposition of collagen and fibronectin in tissues takes place in inflammatory bowel disease, asthma, scleroderma, lupus nephritis, and glomerulonephritis (11)(12)(13)(14). Significant increases in HA and proteoglycans have been observed in rheumatoid arthritis, inflammatory bowel disease, chronic inflammatory vascular disease, lupus nephritis, Graves ophtalmopathy, and type 1 diabetes (15)(16)(17)(18)(19)(20). The marked accumulation of the ECM in human tissues in different diseases and in corresponding experimental animal models (21-24) precedes or coincides with an influx of inflammatory cells, suggesting that the altered ECM influences the trafficking and recruitment of leukocytes into the site of inflammation.…”

Section: Ecm In Inflammationmentioning

confidence: 99%

Thinking Outside the Cell: A Key Role for Hyaluronan in the Pathogenesis of Human Type 1 Diabetes

Bogdani

2016

Diabetes

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Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves' ophthalmopathy

Cited by 121 publications

References 98 publications

Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

Update on thyroid-associated Ophthalmopathy with a special emphasis on the ocular surface

Thinking Outside the Cell: A Key Role for Hyaluronan in the Pathogenesis of Human Type 1 Diabetes

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