scholarly journals Tear Proteomics Approach to Monitoring Sjögren Syndrome or Dry Eye Disease

2019 ◽  
Vol 20 (8) ◽  
pp. 1932 ◽  
Author(s):  
Ming-Tse Kuo ◽  
Po-Chiung Fang ◽  
Tsai-Ling Chao ◽  
Alexander Chen ◽  
Yu-Hsuan Lai ◽  
...  

Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis.

2021 ◽  
Vol 22 (1) ◽  
pp. 422
Author(s):  
Ming-Tse Kuo ◽  
Po-Chiung Fang ◽  
Shu-Fang Kuo ◽  
Alexander Chen ◽  
Yu-Ting Huang

Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye’s performance cannot represent that of the other eye or both eyes. Therefore, in studies for elucidating tear film homeostasis of DED, we may lose some important messages hidden in the fellow eye if we collected clinical and proteomic data only from a unilateral eye. For mechanistic studies, it is recommended that researchers collect tear samples from the eye with more severe DED under sensitive criteria for identifying the more severe eye and evaluating the tear biochemical and proteomic markers with binocular concordance drawn in prior binocular studies.


Author(s):  
G. I. Drozhzhyna ◽  
T. A. Veliksar

The main protective proteins that are synthesized by eye cells are lactoferrin (Lf), lysozyme, immunoglobulin-A, and tear lipocalins. It has been proven that Lf is contained in biological fluids and mucous membranes of various organs; this highlights the importance of this protein in the first line of defense from pathogenic microorganisms. Lf is a non-heme iron-binding chelating glycoprotein from the transferrin family. Lf carries out bactericidal, fungicidal, antiviral, antioxidant and transport functions, prevents the formation of free radicals, inhibits lipid peroxidation, activates enzymes of the antioxidant system. Lf is contained in tears in the highest concentration (about 2 mg/ml, 25% of tear proteins), the average concentration is 1.42 mg/ml. Lf is an important component providing homeostasis of the ocular surface, modulates the activity of T-lymphocytes and macrophages in infections, prevents the multiplication of pathogenic microflora, the development of inflammation, protects the integrity of the cornea, promotes healing from microtraumas, controls the level of iron in the lacrimal fluid, and protects against toxins. These properties of Lf open up prospects for its application in the treatment of chronic diseases of the ocular surface and, in particular, dry eye disease. Lf concentration in tears decreases during sleep, with age, in dry eye disease, keratitis and conjunctivitis, when using contact lenses, that increase the risk of developing eye infections. The first results of the application of ophthalmic drops Lacto (NOVAX® PHARMA) showed good tolerance and therapeutic efficacy in the treatment of inflammatory diseases of the ocular surface. Keywords: lactoferrin, tear, antimicrobial, immunomodulatory, anti-inflammatory properties, ocular surface.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Klemens Fondi ◽  
Kata Miháltz ◽  
Pia Veronika Vécsei-Marlovits

Introduction. The aim of this randomized, observer-masked, parallel group study was to evaluate the short-term and long-term effects of topical hydrocortisone administered in addition to topical ciclosporin A for the first 2 weeks of the treatment in patients with dry eye disease associated with Sjögren syndrome. Materials and Methods. 24 eyes of 12 patients with severe dry eye disease associated with Sjögren syndrome were included in this study. Both eyes of all patients were treated with preservative-free Ciclosporin A eye drops once daily for 6 months. Additionally, one eye of each patient received hydrocortisone eye drops three times daily for the first two weeks of treatment. The study parameters were assessed before treatment, after 2 weeks, and after 6 months of treatment. Results. Tear BUT and corneal fluorescein Oxford staining grade showed significant differences with respect to the baseline when treated with ciclosporin A and hydrocortisone (CsA + Hc) and a nonsignificant increase when treated with ciclosporin A (CsA) alone. After 6 months of treatment, significant increases of tear BUT and corneal Fluorescein Oxford staining grade compared to baseline could be observed in both treatment groups. Aberrometry measurements showed significantly increased optical image quality after 6 months in the CsA + Hc group, while no significant changes could be detected in the eyes treated with CsA alone. However, no significant differences between the two treatment groups could be detected. Discussion. This study indicates that hydrocortisone combined with ciclosporin A therapy may provide fast improvement of clinical symptoms and could have long-term positive effects on the optical image quality in severe DED patients with Sjögren syndrome.


Author(s):  
NITHISH SHEKAR ◽  
D. V. GOWDA ◽  
HITESH KUMAR ◽  
GAURAV K. JAIN ◽  
VIKAS JAIN

At the air-water interface, the tear film lipid layer (TFLL), a combination of lipids and proteins plays an important role in surface tension of the tear and is necessary for the physiological hydration of the ocular surface and maintenance of ocular homeostasis. Alteration in lacrimal fluid rheology, differences in lipid constitution or down regulation of particular tear proteins are found in maximum types of ocular surface disease including dry eye disease (DED). Dry eye is a disorder of the tear film due to tear deficiency or excessive tear evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of discomfort. It results in changes on the ocular surface epithelia causing reduced tear quantity and surface sensitivity which leads to inflammation reactions. Managing this inflammation is very helpful in dry eye disease patients. In this article we revise the current understanding of tear film properties, ocular surface and review the effectiveness of topically applied tear supplements, thermo sensitive atelocollagen punctal plug, subtrasal ultrasonic transducers, novel liposome based gelling tear formation and insulin based ophthalmic delivery systems which help in restoring the healthy tear film.


2021 ◽  
Vol 13 ◽  
pp. 251584142110127
Author(s):  
Preeya K. Gupta ◽  
Nandini Venkateswaran

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film’s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.


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