Topical Cyclosporine in Thyroid Orbitopathy-Related Dry Eye: Clinical Findings, Conjunctival Epithelial Apoptosis, and MMP-9 Expression

Gürdal, Canan; Genç, İpek; Saraç, Özge; Gönül, İpek Işık; Takmaz, Tamer; Can, İzzet

doi:10.3109/02713683.2010.490320

Cited by 60 publications

(44 citation statements)

References 25 publications

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“…[129][130][131] Topical CsA treatment was found to improve thyroid orbitopathy-related dry eye symptoms and decreased MMP-9 expression in conjunctival epithelial cells obtained from patients with thyroid orbitopathy. 132 Results from a retrospective study where patients were treated with 2,000-4,000 mg of oral omega-3 fatty acids and artificial tear replacement with and without CsA emulsion showed that 85% of patients using CsA reported at least 50% improvement in symptoms. About 50% of these showed conversion from a positive to negative InflammaDry test, suggesting that CsA decreased MMP-9 concentration in the tears of these patients.…”

Section: Csamentioning

confidence: 99%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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Dry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. Increased levels and activities of matrix metalloproteinases (MMPs), particularly MMP-9, have been detected in the tears and ocular surface epithelial and inflammatory cells in dry eye. MMPs have been found to participate in disruption of tight junctions in the apical cornea epithelium leading to their accelerated desquamation and barrier disruption. This review summarizes evidence showing the contribution of MMPs to dry eye pathogenesis and their roles as biomarkers and therapeutic targets. Keywords: matrix metalloproteinase, dry eye, keratitis sicca, cornea, barrier function, Sjögren syndrome Dry eye overviewDry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. It affects millions of people worldwide and is one of the most frequent conditions for which patients seek eye care.1 Aging and female sex are significant risk factors for dry eye which increases in prevalence around the fifth decade, with further increase every decade thereafter.2-13 Prevalence of dry eye varies from 2% to 50%, depending on the population studied and the diagnostic criteria for dry eye (symptom questionnaire vs. objective signs). [1][2][3]6,7,[9][10][11][14][15][16][17][18][19][20][21][22][23] There is scarce information about the natural history of dry eye, but there is a recognized disconnection between signs and symptoms; patients tend to be more symptomatic at early stages.24,25 Dry eye causes corneal irregularity [26][27][28] and decreases functional vision by altering contrast sensitivity [29][30][31] and, therefore, decreases quality of life with a significant burden on the individual as well as the society. 23,[32][33][34][35] A meta-analysis of 22 published studies showed increased odds ratio for depression and anxiety in patients with ocular Sjögren syndrome (SS). 36 There is increased evidence that dry eye is an inflammatory disease, and this review will focus on matrix metalloproteinases (MMPs) and their role in the pathogenesis of dry eye. Cornea barrier disruption is a feature of dry eyeAs the principal lens of the eye, the cornea has unique features to maintain its transparency and smooth surface that include a lack of blood vessels and a multilayered stratified, non-cornifying epithelium. The differentiated apical epithelial cells produce

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Section: Csamentioning

confidence: 99%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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“…17 Cellular stress-induced DWm dissipation leads to an aberrant MPTP opening that liberates cytochrome c (Cyt c) release to the cytosol, triggering a cascade of caspase activation that propagates apoptotic signals.cells. 9,12,19,25 We reported that in a canine model of spontaneous DE, apoptosis was increased in conjunctival epithelial cells, whereas it decreased in T cells infiltrating at the same site of inflammation. This was reversed after the dogs were treated topically with 0.2% CsA.…”

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confidence: 99%

Mitochondrial Permeability Transition Pore in Inflammatory Apoptosis of Human Conjunctival Epithelial Cells and T Cells: Effect of Cyclosporin A

Gao

Sana

Calder

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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RESULTS. In IOBA-NHC, TNFa, and IFNc induced MPTP opening, DWm loss, and increased cell apoptosis. This was accompanied by upregulation of Fas/FasL; Bax; and caspase-3, -8, and -9 activation. Addition of CsA prevented IOBA-NHC from cell death by blocking MPTP opening, DWm loss, Fas/FasL, and caspase activation. In PMA/aCD3-activated Jurkat T cells, MPTP opening and DWm loss were increased along with cell apoptosis and upregulated Fas/FasL/ caspase expressions. CsA further promoted T-cell apoptosis, DWm loss, and upregulation of Fas/FasL/caspase. CONCLUSIONS.Inflammation induces aberrant MPTP opening, resulting in an increased apoptosis in conjunctival epithelial cells. CsA protected IOBA-NHC from cell death by blocking both intrinsic and extrinsic apoptosis pathways. CsA promoted T-cell apoptosis via upregulating Fas/FasL and caspase activities with a minimal effect on MPTP. The findings suggest that the differential effect of CsA on T cells versus ocular surface resident epithelial cells may contribute to its therapeutic efficacy in treating ocular inflammation such as dry eye disease.

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“…This implies that inflammation may be involved in the pathogenesis of dry eye associated with TO. In addition, anti-inflammatory or anti-cytokine therapy may be effective for the treatment of such cases (Brignole et al, 2000;Pflugfelder, 2004;De Paiva et al, 2006;Cordero-Coma et al, 2007;Kymionis et al, 2008;Pflugfelder et al, 2008;Ridder, 2008;Goyal et al, 2009;Gürdal et al, 2010). Anti-TNF-a agents, cytokine receptor antibodies, and IFN-a2a are the routinely used biologics (Jap and Chee, 2008).…”

Section: Discussionmentioning

confidence: 99%

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

Hsu¹,

Lee²,

Chang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL-6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TOrelated dry eye or other ocular surface inflammatory disorders.

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Topical Cyclosporine in Thyroid Orbitopathy-Related Dry Eye: Clinical Findings, Conjunctival Epithelial Apoptosis, and MMP-9 Expression

Abstract: Topical CsA treatment appears to improve the signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in conjunctival epithelial cells in TO-related dry eye patients after 2 months of treatment.

Cited by 60 publications

References 25 publications

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Mitochondrial Permeability Transition Pore in Inflammatory Apoptosis of Human Conjunctival Epithelial Cells and T Cells: Effect of Cyclosporin A

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

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