Electrostatic and Covalent Assemblies of Anionic Hydrogel-Coated Gold Nanoshells for Detection of Dry Eye Biomarkers in Human Tears.
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ABSTRACT:
SUBMITTER: Wechsler ME
PROVIDER: S-EPMC8588787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To investigate the expression, release, and proteolytic degradation of galectin-3 in patients with dry eye disease.Observational case series with a comparison group.Tear washes and conjunctival impression cytology specimens were collected through standard procedures from 16 patients with dry eye and 11 age-matched healthy subjects. Galectin-3 content in tears was analyzed by quantitative Western blot, using recombinant galectin-3 protein to generate a calibration curve. The relative expression of galectin-3 and matrix metalloproteinase 9 (MMP9) was evaluated by quantitative polymerase chain reaction. The cleavage of galectin-3 was studied in vitro using activated recombinant MMP9 and protease inhibitors.The concentration of galectin-3 protein in tears, but not galectin-3 expression in conjunctival epithelium, was significantly higher in tears of patients with dry eye (0.38 ng/?g total protein, range 0.04-1.36) compared to healthy subjects (0.12 ng/?g total protein, range 0.00-0.41) (P < .01). By Western blot, an intact (?28.0 kDa) galectin-3 band was identified in tear samples from healthy subjects, whereas 50% of the dry eye samples were characterized by the additional presence of a partially degraded form (?25.4 kDa). In our experiments, elevated expression of MMP9 in dry eye subjects correlated with the ability of active MMP9 to cleave galectin-3 from recombinant origin. Interestingly, cleavage of endogenous galectin-3 in tear samples was impaired using a broad-spectrum proteinase inhibitor cocktail, but not the pan-specific MMP inhibitor GM6001, suggesting the presence of proteases other than MMPs in promoting galectin-3 degradation in dry eye.Our results indicate that release of cellular galectin-3 into tears is associated with epithelial dysfunction in dry eye, and that galectin-3 proteolytic cleavage may contribute to impaired ocular surface barrier function.
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Project description:PurposeO-linked carbohydrates (O-glycans) contribute to the hydrophilic character of mucins in mucosal tissues. This study was conducted to identify the repertoire of O-glycans in the tear film and the glycosyltransferases associated with their biosynthesis, in normal subjects and patients with non-Sjögren's dry eye.MethodsHuman tear fluid was collected from the inferior conjunctival fornix. O-glycans were released by hydrazinolysis, labeled with 2-aminobenzamide, and analyzed by fluorometric, high-performance liquid chromatography (HPLC) coupled with exoglycosidase digestions. O-glycan structures identified in tears were related to potential biosynthetic pathways in human conjunctival epithelium by using a glycogene microarray database. Lectin-binding analyses were performed with agglutinins from Arachis hypogaea, Maackia amurensis, and Sambucus nigra.ResultsThe O-glycan profile of human tears consisted primarily of core 1 (Gal beta 1-3GalNAc alpha 1-Ser/Thr)-based structures. Mono-sialyl O-glycans represented approximately 66% of the glycan pool, with alpha2-6-sialyl core 1 being the predominant O-glycan structure in human tears (48%). Four families of glycosyltransferases potentially related to the biosynthesis of these structures were identified in human conjunctiva. These included 13 polypeptide-GalNAc-transferases (GALNT), the core 1 beta-3-galactosyltransferase (T-synthase), three alpha2-6-sialyltransferases (ST6GalNAc), and two alpha2-3-sialyltransferases (ST3Gal). No significant differences in total amount of O-glycans were detected between tears of normal subjects and patients with dry eye, by HPLC and lectin blot. Likewise, no differences in glycosyltransferase expression were found by glycogene microarray.ConclusionsThis study identified the most common mucin-type O-glycans in human tears and their expected biosynthetic pathways in ocular surface epithelia. Patients with non-Sjögren's dry eye showed no alterations in composition and amount of O-glycans in the tear fluid.
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Project description:The aims of this study were to determine if histatin-1 (H1) is present in normal human tears and whether tear levels of H1 varied between normal patients and those with aqueous deficient dry eye disease (ADDE). Patient samples were obtained from 11 normal patients and 11 severe ADDE patients. Relevant patient characteristics, including age, sex, and dry eye disease (DED) diagnostic parameters were collected. Multiple qualitative and quantitative methods were used to compare the concentration of H1 between patient groups. Mixed linear modeling was used to compare H1 levels between groups, and diagnostic performance was assessed using the receiver-operator-characteristic (ROC). ADDE patients had significantly lower H1 concentrations (85.9 ± 63.7 ng/ml) than the normal group (891.6 ± 196.5 ng/ml) (p < 0.001), while controlling for age and sex. ROC analysis indicated that H1 concentration is potentially a biomarker for ADDE (area under curve = 0.96). Reclassification of patients by DED parameters including, Ocular Surface Disease Index (OSDI) (≤13, >13) and Schirmer I (without anesthesia) (<10 mm, ≥10 mm) showed significant differences in H1 level (OSDI, p = 0.004) and Schirmer I ((p = 0.010). In conclusion, this is the first preliminary report of the presence of H1 in human tears. H1 concentrations are lower in ADDE patients and H1 may have diagnostic potential in evaluation ADDE patients.
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Project description:Dry Eye Disease (DED) is part of several conditions, including Sjögren's syndrome (SS) and no single test to diagnosis DED. The present study intends to evaluate whether a set of signs and symptoms of DED can distinguish: a) SS from other non-overlapping systemic diseases related to DED; b) primary and secondary SS. 182 consecutive patients with DED were evaluated under five groups: SS, graft-versus-host disease (GVHD), Graves' orbitopathy (GO), diabetes mellitus (DM), glaucoma under treatment with benzalkonium chloride medications (BAK). Twenty-four healthy subjects were included as control group (CG). The evaluation consisted of Ocular Surface Disease Index (OSDI), Schirmer test (ST), corneal fluorescein staining (CFS) and tear film break up time (TFBUT). Indeed, a subset of DED patients (n = 130), classified as SS1, SS2 and nonSS (NSS) by the American-European Criteria were compared. Quadratic discriminant analysis (QDA) classified the individuals based on variables collected. The area under Receiver Operating Characteristics (ROC) curve evaluated the classification performance in both comparisons. Comparing SS with other diseases, QDA showed that the most important variable for classification was OSDI, followed by TFBUT and CFS. Combined, these variables were able to correctly classify 62.6% of subjects in their actual group. At the discretion of the area under the ROC curve, the group with better classification was the control (97.2%), followed by DM (95.5%) and SS (92.5%). DED tests were different among the NSS, SS1 and SS2 groups. The analysis revealed that the combined tests correctly classified 54.6% of the patients in their groups. The area under the ROC curve better classified NSS (79.5%), followed by SS2 (74.4%) and SS1 (69.4%). Diseases that causes DED, and also SS1, SS2 and NSS are distinguishable conditions, however a single ocular tools was not able to detect the differences among the respective groups.
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Project description:IntroductionThe present study aimed to compare the effects of rebamipide and artificial tears during the perioperative period of cataract surgery on the postoperative visual outcomes.MethodsSeventy-two eyes from 36 patients with a cataract were enrolled. Rebamipide (group R) was administered in one eye and Mytear® artificial tear ophthalmic solution (group A) in the other eye from 4 weeks preoperatively to 3 months postoperatively. Tear breakup time (TBUT), high-order aberrations (HOAs), superficial punctate keratopathy in the central part of the cornea (C-SPK), and corrected distance visual acuity (CDVA) were assessed at baseline, 1 week, 1 month, and 3 months after cataract surgery with trifocal intraocular lens (IOL) implantation. Contrast sensitivity and disability glare with visual angle values compatible with spatial frequencies of 1.1, 1.8, 2.9, 4.5, 7.1, and 10.2 cycles/degree (CPD) were evaluated postoperatively. Between-group differences of all variables were analyzed.ResultsAt baseline, no significant differences in the variables were noted between the two groups. Mean TBUT was significantly higher, while mean C-SPK and HOAs were significantly lower in group R than in group A at each assessment. Mean CDVA was significantly higher at 1 week and 1 month postoperatively in group R compared with group A; this value was not significant at 3 months. Between-group differences in contrast sensitivity and disability glare were statistically significant at all spatial frequencies, 1 week and 1 month postoperatively. At 3 months postoperatively, there were significant differences in contrast sensitivity and disability glare at most spatial frequencies.ConclusionDry eye management with rebamipide in the perioperative period of cataract surgery with trifocal IOL implantation was significantly more effective than artificial tears in improving ocular surface condition, contrast sensitivity, and disability glare postoperatively.
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