The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Stephen C Pflugfelder - One of the best experts on this subject based on the ideXlab platform.
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the pathophysiology of dry eye disease what we know and future directions for research
Ophthalmology, 2017Co-Authors: Stephen C Pflugfelder, Cintia S De PaivaAbstract:Clinical and laboratory studies performed over the past few decades have discovered that dry eye is a chronic inflammatory disease that can be initiated by numerous extrinsic or intrinsic factors that promote an unstable and hyperosmolar Tear film. These changes in Tear Composition, in some cases combined with systemic factors, lead to an inflammatory cycle that causes ocular surface epithelial disease and neural stimulation. Acute desiccation activates stress signaling pathways in the ocular surface epithelium and resident immune cells. This triggers production of innate inflammatory mediators that stimulate the production of matrix metalloprotease, inflammatory cell recruitment, and dendritic cell maturation. These mediators, combined with exposure of autoantigens, can lead to an adaptive T cell-mediated response. Cornea barrier disruption develops by protease-mediated lysis of epithelial tight junctions, leading to accelerated cell death; desquamation; an irregular, poorly lubricated cornea surface; and exposure and sensitization of epithelial nociceptors. Conjunctival goblet cell dysfunction and death are promoted by the T helper 1 cytokine interferon gamma. These epithelial changes further destabilize the Tear film, amplify inflammation, and create a vicious cycle. Cyclosporine and lifitegrast, the 2 US Food and Drug Administration-approved therapies, inhibit T-cell activation and cytokine production. Although these therapies represent a major advance in dry eye therapy, they are not effective in improving discomfort and corneal epithelial disease in all patients. Preclinical studies have identified other potential therapeutic targets, biomarkers, and strategies to bolster endogenous immunoregulatory pathways. These discoveries will, it is hoped, lead to further advances in diagnostic classification and treatment.
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dry eye as a mucosal autoimmune disease
International Reviews of Immunology, 2013Co-Authors: Michael E Stern, Chris S Schaumburg, Stephen C PflugfelderAbstract:Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters Tear Composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal Tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface.
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production and activity of matrix metalloproteinase 9 on the ocular surface increase in dysfunctional Tear syndrome
Investigative Ophthalmology & Visual Science, 2009Co-Authors: S Chotikavanich, Cintia S De Paiva, Joseph J Chen, Fang Bian, William J Farley, Stephen C PflugfelderAbstract:It has been proposed that inflammatory mechanisms are involved in the pathophysiology of dysfunctional Tear syndrome (DTS), the more encompassing term for dry eye disease, proposed by the Delphi Dry Eye Panel Report in 2006.1 It is now recognized that changes in Tear Composition in DTS may destabilize the Tear film and cause ocular surface epithelial disease.1,2–6 Matrix metalloproteinases (MMPs) are proteolytic enzymes produced by stressed ocular surface and glandular epithelial cells, as well as by the inflammatory/immune cells that infiltrate these tissues. Increased activity of MMPs has been implicated in these pathologic ocular surface changes.5,7 MMPs play a vital role in wound healing and inflammation.8,9 Increased levels of MMP-3 and -9 have been detected in the Tear fluid of patients with keratoconjunctivitis sicca (KCS).10,11 Among the MMPs, MMP-9 has been found to be of central importance in cleaving epithelial basement membrane components and tight junction proteins (such as ZO-1 and occludin) that maintain corneal epithelial barrier function.12–14 MMP-9 belongs to the gelatinase group of metalloproteinases that degrade denatured collagen; native collagens type IV, V, and VII; and elastin. Expression of MMP-9 by the ocular surface epithelia in normal healthy eyes is low.15 Increased production of MMP-9 by the corneal epithelium has been found in the eyes of individuals with sterile corneal ulceration.16 Increased MMP-9 activity has been associated with disruption of corneal epithelial barrier function and corneal surface irregularity in an experimental murine model of dry eye.17 MMP-9 knockout mice showed significantly less alteration of epithelial barrier function in response to experimental desiccating stress than did wild-type mice.17 This protective effect was abrogated by topical application of MMP-9 to the ocular surface.17 Previous human studies have found an increased concentration of pro-MMP-9 measured by enzyme-linked immunosorbent assay (ELISA) in Tear fluid of patients with ocular rosacea.5,10 Solomon et al.4 found increased activity of MMP-9 in the Tear fluid of patients with meibomian gland disease and Sjogren’s syndrome.4 Most MMPs are secreted as inactive zymogens (proMMPs) that require extracellular activation before they are able to cleave extracellular matrix components. This study was designed to measure the activity of the total active form of MMP-9 in normal eyes and in those in the various DTS groups classified by the Delphi panel and the Dry Eye Workshop (DEWS). The correlation between Tear MMP-9 activity and clinical parameters of DTS was determined. Finally, mRNA transcript levels of MMP-9 and its regulating cytokines in the conjunctival epithelium were measured.
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Inflammation in Dry Eye
Ocular Surface, 2004Co-Authors: Michael E Stern, Stephen C PflugfelderAbstract:Abstract Dry eye is a condition of altered Tear Composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the Tear-secreting glands. Changes in Tear Composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.
Chika Shigeyasu - One of the best experts on this subject based on the ideXlab platform.
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diquafosol sodium ophthalmic solution for the treatment of dry eye clinical evaluation and biochemical analysis of Tear Composition
Japanese Journal of Ophthalmology, 2015Co-Authors: Chika Shigeyasu, Masakazu Yamada, Yoko AkuneAbstract:Purpose To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of Tear proteins and mucin-like substances after the treatment.
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diquafosol sodium ophthalmic solution for the treatment of dry eye clinical evaluation and biochemical analysis of Tear Composition
Japanese Journal of Ophthalmology, 2015Co-Authors: Chika Shigeyasu, Yoko Akune, Masakazu Yamada, Kazuo TsubotaAbstract:To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of Tear proteins and mucin-like substances after the treatment. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were Tear osmolarity, Tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major Tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including Tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in Tear proteins. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the Tears of patients with dry eye.
Stefano Bonini - One of the best experts on this subject based on the ideXlab platform.
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age related changes to human Tear Composition
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Alessandra Micera, Antonio Di Zazzo, Graziana Esposito, Rosa Longo, William Foulsham, Roberto Sacco, R Sgrulletta, Stefano BoniniAbstract:Purpose We characterize age-associated alterations in the expression of inflammatory mediators and tissue remodeling factors in human Tears. Methods A total of 75 consecutive volunteers (32 male/44 female; 19-93 years) underwent clinical assessment of ocular surface status, ocular surface disease index (OSDI) grading and Tear sampling. The volunteers were categorized into three groups: young (18-40 years), middle-aged (41-60 years), and old (>60 years). Total protein profiles and chip-based protein array evaluations were conducted to investigate the expression of 60 potential candidates, including pro-/anti-inflammatory mediators and tissue remodeling factors. Appropriate validations were performed using conventional assays. Multiple comparisons for regression between potential candidates and age were performed, as well as statistical analyses among the three age groups. Nonpooled samples were used for quantifications. Results Pearson analysis of chip-arrays identified 9 of 60 potential candidates. Specifically, IL-8, IL-6, and regulated on activation, normal T cell expressed and secreted (RANTES; P < 0.0083) protein as well as matrix metalloproteinase (MMP)-1, IL-3, and TNF-α (P < 0.05) correlated positively with aging. MIP-3β showed an opposite tendency. Western blot and ELISA analysis corroborated the array data. OSDI grading did not correlate with aging. Conclusions Dynamic changes to Tear protein profiles occur with aging. Our study identifies the expression of IL-8, IL-6, RANTES, MMP-1, and MIP-3β as increasing with age. These select inflammatory and matrix remodeling factors may be relevant to the development of novel diagnostic tools and therapeutics in the context of age-related ocular surface disease.
Scott M Gouveia - One of the best experts on this subject based on the ideXlab platform.
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age related changes in human Tear Composition and stability
Cornea, 2000Co-Authors: John M Tiffany, Scott M GouveiaAbstract:The preocular Tear film is involved in physical protection, corneal nutrition, lid lubrication and refraction of light entering the eye. With each blink the Tear film is reformed, so it needs to be stable when the eyes are open between blinks. Tear film stability is dependent on its physical properties, in particular surface tension and viscosity.1,2
Yoko Akune - One of the best experts on this subject based on the ideXlab platform.
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diquafosol sodium ophthalmic solution for the treatment of dry eye clinical evaluation and biochemical analysis of Tear Composition
Japanese Journal of Ophthalmology, 2015Co-Authors: Chika Shigeyasu, Masakazu Yamada, Yoko AkuneAbstract:Purpose To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of Tear proteins and mucin-like substances after the treatment.
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diquafosol sodium ophthalmic solution for the treatment of dry eye clinical evaluation and biochemical analysis of Tear Composition
Japanese Journal of Ophthalmology, 2015Co-Authors: Chika Shigeyasu, Yoko Akune, Masakazu Yamada, Kazuo TsubotaAbstract:To evaluate the clinical efficacy of 3 % diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of Tear proteins and mucin-like substances after the treatment. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were Tear osmolarity, Tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major Tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including Tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in Tear proteins. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the Tears of patients with dry eye.
