Laboratory findings in tear fluid analysis

Ohashi, Yutaro; Doğru, Murat; Tsubota, Kazuo

doi:10.1016/j.cca.2005.12.035

Cited by 196 publications

(136 citation statements)

References 105 publications

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“…For patients, the inclusion criteria were a Schirmer test I value higher than 10 mm/5 min, a tear film break-up time (TFBUT) value p10 s, mild subjective symptoms of ocular discomfort as evaluated by an OSDI questionnaire 11 (score [12][13][14][15][16][17][18][19][20][21][22][23][24], and use of tear substitutes only, for treatment, which were suspended for at least 3 days before tear collection.…”

Section: Subjectsmentioning

confidence: 99%

Tear proteomics in evaporative dry eye disease

Versura

Nanni

Bavelloni

et al. 2010

Eye

142

114

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Purpose: To analyze tear protein variations in patients suffering from dry eye symptoms in the presence of tear film instability but without epithelial defects. Methods: Five microlitres of non-stimulated tears from 60 patients, suffering from evaporative dry eye (EDE) with a break-up time (BUT) o10 s, and from 30 healthy subjects as control (no symptoms, BUT 410 s) were collected. Tear proteins were separated by mono and bi-dimensional SDS-PAGE electrophoresis and characterized by immunoblotting and enzymatic digestion. Digested peptides were analyzed by liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry followed by comparative data analysis into Swiss-Prot human protein database using Mascot. Statistical analysis were performed by applying a t-test for independent data and a MannWhitney test for unpaired data (Po0.05). Results: In EDE patients vs controls, a significant decrease in levels of lactoferrin (data in % ± SD): 20.15 ± 2.64 vs 24.56 ± 3.46 (P ¼ 0.001), lipocalin-1: 14.98±2.70 vs 17.73±2.96 (P ¼ 0.0001), and lipophilin A-C: 2.89±1.06 vs 3.63±1.37 (P ¼ 0.006) was revealed, while a significant increase was observed for serum albumin: 9.45 ± 1.87 vs 3.46 ± 1.87 (P ¼ 0.0001). No changes for lysozyme and zinc a-2 glycoprotein (P ¼ 0.07 and 0.7, respectively) were shown. Proteomic analysis showed a downregulation of lipophilin A and C and lipocalin-1 in patients, which is suggested to be associated with post-translational modifications. Conclusions: Data show that tear protein changes anticipate the onset of more extensive clinical signs in early stage dry eye disease.

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Section: Subjectsmentioning

confidence: 99%

Tear proteomics in evaporative dry eye disease

Versura

Nanni

Bavelloni

et al. 2010

Eye

142

114

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“…[19][20] The average rate of tear product is in the range of 0.5-2.2 µl/min; about 0.72-3.2 ml of tears are secreted per day. 21 Tear fluid normally consists of over 20 components, including salt water, proteins, glucose, some small metallic ions, etc. 21 Tear glucose has been studied since 1930.…”

Section: Introductionmentioning

confidence: 99%

“…21 Tear fluid normally consists of over 20 components, including salt water, proteins, glucose, some small metallic ions, etc. 21 Tear glucose has been studied since 1930. 22 Many reports have demonstrated that tear glucose is higher in diabetic subjects than in healthy ones.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose

Zhang

Hodge

Hutnick

et al. 2011

J Diabetes Sci Technol

137

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This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels-almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently.

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“…В последние годы исследование протеома сле-зы вызывает все больший интерес [58,69,97,98]. Все больше научных данных указывают на то, что анализ белкового состава слезы является перспек-тивным направлением исследований его примени-мости для раннего распознавания офтальмологиче-ской патологии.…”

Section: рис 3 структура слезной пленкиunclassified

Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

et al. 2017

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The paper presents epidemiologic and pathophysiological aspects of the problem statement for early recognition of Uveitis (Uv) associated with Juvenile Idiopathic Arthritis (JIA) in terms of the proteomic profile of tears as well as the results of an attempt to solve this problem by means of the Tandem Mass-Spectrometry (TMS). The solution of this problem is of the highest relevance due to revolutionary changes in treatment strategies after introducing highly effective biologics. Content analysis of literature reviews reveals the following: 1. the incidence of JIA-Uv in the Northwest Federal District of Russian Federation averages 0.5-0.7 per 100 000 of children with the prevalence being ten-fold higher than incidence, 2. without Methotrexate treatment 4-7 years after the diagnosis of JIA-Uv cataract is revealed in 35-40% of children and in 5% – glaucoma as well, 3. even with Methotrexate in 28-40% of children the complications of JIA-Uv inevitably will be revealed with blurred vision in 10-36% of children, 4. timely diagnosis of JIA-Uv and adequate treatment reduce the risk of complications by 4% per year, 5. current medical care system reveals in one third of children already the complications of JIA-Uv. Revelation in tears of the motif mode for protein interaction network, triggering mobilization/inhibition of cells which moderate Uv would contradict the traditional point of view on existing natural anatomic and physiologic barriers, isolating the intraocular space, but however seems to be possible since JIA is a systemic disease and Uv leads to damage of the blood-retinal barriers. To reveal protein biomarkers of JIA-Uv tears of 31 children aged 2-17 years were studied: 17 – chronic JIA-Uv, 4 – JIA without Uv, 4 – idiopathic Uv, 3 – systemic vasculitis, 3 – healthy children. We used the current clinical guidelines and standards to diagnose the pathology and TMS with hierarchical clustering methodology for protein identification: nano C18 column attached to Shimadzu nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer, data-dependent 4-event scan method, a survey FT-MS parent scan followed by sequential data dependent FT-MS/MS scans on the three most abundant peptide ions. Proteins were identified from the mass spectra results with Proteome Discoverer 1.2 software for protein database search using the International Protein Index (IPI) and Human Protein Database. Quantification was conducted using SIEVE 2.0 after normalization to albumin keeping in mind the validity of proportional change of its concentration after stimulation of lacri-mation. Data from SIEVE were exported to IPA (Ingenuity Pathway Analysis) for filtering. The extracellular proteins selected in Ingenuity were further analyzed for disease relation and networks formation. TMS revealed more than 3000 proteins in tears and 300 of them have been considered to be the first row candidates to be biomarkers of JIA-Uv. The top two proteins, lactoferrin and lipocalin were upregulated over ten-fold in children with Uv. Pathway analysis placed these proteins into the inflammation-related IL-1 and TNF-α related networks which also included proteins involved in the development of endothelial dysfunction, inflammation and retinopathy. In addition, IL-23, which was previously linked to Uveitis, was found to be upregulated. Taken together, our proof-of-principle study presents a novel and yet untested approach for detection of early biomarkers of Uveitis and identified several candidate proteins.

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Laboratory findings in tear fluid analysis

Cited by 196 publications

References 105 publications

Tear proteomics in evaporative dry eye disease

Tear proteomics in evaporative dry eye disease

Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose

Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

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