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Clinical & Translational Immunology 2021SARS-CoV-2 can be transmitted by aerosols, and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to...
OBJECTIVES
SARS-CoV-2 can be transmitted by aerosols, and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed the SARS-CoV-2-specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination.
METHODS
We measured the antibody responses in 16 subjects with COVID-19 infection for an average of 7 months before, and 15 subjects before and 2 weeks post-Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Eleven pre-pandemic individuals were included as healthy controls.
RESULTS
IgG antibodies to spike and nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison with uninfected controls. While receptor-binding domain (RBD)-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. By contrast, high levels of IgG antibodies to spike and RBD, but not nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination but were unchanged in tears and saliva. Comirnaty vaccination induced high neutralising Abs in the plasma, but limited neutralising antibodies were detected in saliva or tears.
CONCLUSION
Both infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests the neutralising antibodies may be low in the tears late following infection.
PubMed: 34754451
DOI: 10.1002/cti2.1354 -
Veterinary Sciences Feb 2021Tear film provides lubrication and protection to the ocular surface. The sedation reduces tear production, often leading to perioperative exposure keratopathy. The aim...
Tear film provides lubrication and protection to the ocular surface. The sedation reduces tear production, often leading to perioperative exposure keratopathy. The aim of the present study was to report the effects of intramuscular dexmedetomidine on canine tear production, measured by STT-1, for an experimental period of 8 h after sedation. Ten dogs who underwent sedation for routine radiologic assessment were recruited for the study. In all animals, tear production in right and left eyes was measured 15 min before sedation (T0: basal values) and 20 min (T20), 1 h (T1), 2 h (T2), 4 h (T4) and 8 h (T8) after drug administration. Analysis of variance and post hoc Bonferroni test ( < 0.05) were performed. A significant effect of time on canine tear production was found. The tear production returned to basal values at T8. So, it is recommended to treat the canine eyes with tear substitutes during and up to 12 h after sedation.
PubMed: 33669215
DOI: 10.3390/vetsci8020028 -
Eye (London, England) Jun 2022To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI)... (Observational Study)
Observational Study
OBJECTIVES
To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer.
METHODS
This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman's and Post-hoc Dunn tests were used for the statistical analysis.
RESULTS
TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p < 0.001, p = 0.023, p < 0.001, p = 0.01, p = 0.002, p = 0.004, p < 0.001, p < 0.001), and meiboscore, CS, OSDI scores and sub-basal nerve tortuosity values were increased (p < 0.001, p = 0.015, p = 0.001, p = 0.004) during the treatment. Endothelial pleomorphism rates were lower at the 3- and 6-month timepoints compared to before the treatment (p = 0.04).
CONCLUSION
This study showed that aromatase inhibitor therapy causes deteriorations in many of the ocular-surface parameters and corneal structural changes in relation with the duration of treatment. These patients should be observed during the therapy in terms of the ocular-surface side effects.
Topics: Aromatase Inhibitors; Cornea; Dry Eye Syndromes; Humans; Meibomian Glands; Prospective Studies; Tears
PubMed: 34117393
DOI: 10.1038/s41433-021-01612-z -
Scientific Reports Mar 2019The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported...
The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading and decreased tear secretion, we established a stress-induced DED mouse model, which permitted us to address the underlying mechanism of pathogenesis and resilience. Enriched environment (EE) was an effective intervention to prevent and alleviate stress-induced decreased tear secretion. Because stress loading resulted in decreased brain-derived neurotrophic factor (BDNF) expression while EE resulted in increased expression, we focused on the role of BDNF in tear secretion. Using two distinct Bdnf gene knockdown mice, we evaluated whether BDNF was a deterministic factor in regulating tear secretion in healthy and stressed conditions. Bdnf knockdown mice showed decreased basal tear secretion and loss of stress tolerance by EE for tear secretion. These results suggest that BDNF expression is related to tear secretion and to the pathology of DED.
Topics: Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Dry Eye Syndromes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Tears
PubMed: 30833600
DOI: 10.1038/s41598-019-39467-w -
Investigative Ophthalmology & Visual... Aug 2011Lacritin is a novel human tear glycoprotein that promotes basal tear peroxidase secretion by rat lacrimal acinar cells in vitro. This study investigates whether lacritin...
PURPOSE
Lacritin is a novel human tear glycoprotein that promotes basal tear peroxidase secretion by rat lacrimal acinar cells in vitro. This study investigates whether lacritin is prosecretory when added topically to the ocular surface of normal living rabbits, and if so, what is its efficacy and tolerability versus cyclosporine and artificial tears.
METHODS
Purified recombinant human lacritin (1, 10, 50, or 100 μg/mL), inactive lacritin truncation mutant C-25 (10 μg/mL), cyclosporine (0.05%), or artificial tears were topically administered to eyes of normal New Zealand White rabbits either as a single dose or three times daily for 14 days with monitoring of basal tear production. Basal tearing under proparacaine anesthesia was repeatedly assessed throughout and 1 week after chronic treatment ceased. Eyes were examined weekly by slit-lamp biomicroscopy.
RESULTS
Lacritin acutely increased basal tearing to 30% over vehicle at 240 minutes. Three times daily treatment with 10-100 μg/mL lacritin was well tolerated. Basal tearing became progressively elevated 4, 7, and 14 days later and was 50% over baseline (50 μg/mL lacritin) 1 week after treatment had ceased. Cyclosporine elevated tearing to a similar level on days 4 and 7 but had little or no effect on day 14 and had returned to baseline 1 week after ending treatment. C-25 and artificial tears had no effect.
CONCLUSIONS
Lacritin acutely stimulates basal tear flow that is sustained for at least 240 minutes. Two weeks of lacritin treatment three times daily was well tolerated and progressively elevated the basal tear flow. One week after treatment ended, basal tearing was still 50% over baseline. In contrast, cyclosporine triggered mild to moderate corneal irritation and a temporary elevation in tearing.
Topics: Administration, Topical; Animals; Cyclosporine; Eye Proteins; Glycoproteins; Intraocular Pressure; Lacrimal Apparatus; Ophthalmic Solutions; Rabbits; Recombinant Proteins; Tears; Time Factors; Tonometry, Ocular
PubMed: 21087963
DOI: 10.1167/iovs.10-6220 -
Journal of Ophthalmology 2023We aim to investigate the effect of overexposure to blue light on the rat ocular surface and explore the potential mechanisms. 450 nm light-emitting diode (LED)...
We aim to investigate the effect of overexposure to blue light on the rat ocular surface and explore the potential mechanisms. 450 nm light-emitting diode (LED) derived light at 1000 lux was used to irradiate SD rats, 12 hours a day, for consecutive 28 days. Rats in the control group were exposed to 400 lux white light at the same time (in an indoor environment). Tear film breakup time (TBUT), tear volume, and corneal fluorescein staining scores were used to measure the changes to the ocular surface. Expressions of nuclear factor-B (NF-B), inhibitor-B (I-B), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) were measured by real-time PCR, and the activation of the NF-B pathway was detected by Western blotting, respectively. Cornea ultrastructure was examined by TEM and optical microscope on day 28. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-B signaling pathway, was used to measure the inhibition of blue light injury. The above indexes were detected again when compared with the solvent-treated group. On day 28, compared with day 0, the TBUT of the blue light group was significantly shorter, and the score was significantly higher. The amount of tear secretion changed slightly with time. HE and PAS staining revealed significantly decreased corneal epithelial cell layers and increased goblet cells after 28-day irradiation of blue light. Disarranged stromal cells, vacuoles in the basal nuclei, and decreased desmosomes were also found in the blue light group. Significantly increased levels of NF-B, IL-6, TNF-, and the ratio of phosphorylated NF-B p65 (pNF-B p65) to total NF-B p65 implied blue light-induced damage and pathway activation. In addition, PDTC significantly reduced the phosphorylation of NF-B activated in blue light-treated corneas and alleviated the ocular surface changes caused by blue light. Finally, our results demonstrated that long-term blue light exposure in rats could cause ocular surface changes and manifest as dry eye. Inflammation and activation of the NF-B pathway may play a role in the pathogenesis.
PubMed: 36660316
DOI: 10.1155/2023/1097704 -
Frontiers in Neuroscience 2023The intraepithelial sub-basal nerve plexus of the cornea is characterized by a central swirl of nerve processes that terminate between the apical cells of the...
The intraepithelial sub-basal nerve plexus of the cornea is characterized by a central swirl of nerve processes that terminate between the apical cells of the epithelium. This plexus is a critical component of maintaining homeostatic function of the ocular surface. The cornea contains a high concentration of collagen, which is susceptible to damage in conditions such as neuropathic pain, neurotrophic keratitis, and dry eye disease. Here we tested whether topical application of a collagen mimetic peptide (CMP) is efficacious in repairing the corneal sub-basal nerve plexus in a mouse model of ocular surface desiccation. We induced corneal tear film reduction, epithelial damage, and nerve bed degradation through a combination of environmental and pharmaceutical (atropine) desiccation. Mice were subjected to desiccating air flow and bilateral topical application of 1% atropine solution (4× daily) for 2 weeks. During the latter half of this exposure, mice received topical vehicle [phosphate buffered saline (PBS)] or CMP [200 μm (Pro-Pro-Gly), 10 μl] once daily, 2 h prior to the first atropine treatment for that day. After euthanasia, cornea were labeled with antibodies against βIII tubulin to visualize and quantify changes to the nerve bed. For mice receiving vehicle only, the two-week desiccation regimen reduced neuronal coverage of the central sub-basal plexus and epithelial terminals compared to naïve, with some corneas demonstrating complete degeneration of nerve beds. Accordingly, both sub-basal and epithelial βIII tubulin-labeled processes demonstrated increased fragmentation, indicative of nerve disassembly. Treatment with CMP significantly reduced nerve fragmentation, expanded both sub-basal and epithelial neuronal coverage compared to vehicle controls, and improved corneal epithelium integrity, tear film production, and corneal sensitivity. Together, these results indicate that topical CMP significantly counters neurodegeneration characteristic of corneal surface desiccation. Repairing underlying collagen in conditions that damage the ocular surface could represent a novel therapeutic avenue in treating a broad spectrum of diseases or injury.
PubMed: 37260844
DOI: 10.3389/fnins.2023.1148950 -
Saudi Journal of Ophthalmology :... 2023The purpose of this study is to evaluate the tear secretion and ocular surface properties in children with Graves' ophthalmopathy (GO) and to compare the results with...
PURPOSE
The purpose of this study is to evaluate the tear secretion and ocular surface properties in children with Graves' ophthalmopathy (GO) and to compare the results with those of healthy children.
METHODS
This was a cross-sectional study. Forty-three patients with GO (Group 1) and 41 healthy children without any ocular and/or systemic disorder (Group 2) were examined clinically and underwent tests for dry eye. We performed analyses including the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test under topical anesthesia (<5 mm was abnormal), slit-lamp biomicroscopy (corneal fluorescein staining and tear breakup time (TBUT) under blue-light illumination), and fundoscopic evaluation.
RESULTS
Dry eye symptoms and the mean OSDI score were significantly ( < 0.02) higher (15.6 ± 18.7) in patients with GO compared with controls (5.67 ± 3.6). The mean Schirmer's (basal tear secretion) tests value was significantly reduced in Group 1 (5.25 ± 3.1 mm) compared with Group 2 (17.1 ± 5.2), respectively. The difference was statistically significant (p < 0.005), suggesting inadequate tear production. The mean tear film breakup time in children was lower in patients with GO (8.3 ± 3.42 s,) compared with controls (13.2 ± 4.74 s), ( < 0.001) suggesting an unstable tear film. Decrease of corneal sensitivity (23.3%) was noted in patients with GO compared with controls. GO patients showed a significant increase of the frequency of corneal fluorescein staining (6.9%) in patients with GO compared with controls.
CONCLUSION
Patients with GO had a statistically significant higher incidence of dry eye symptoms and the increase of OSDI score. Significantly lower Schirmer's and TBUT tests results were seen in the study group when compared with the controls. These findings may indicate a tendency for dry eye in pediatric GO patients.
PubMed: 37492217
DOI: 10.4103/sjopt.sjopt_47_22 -
American Journal of Translational... 2016The purpose of the present study was to assess the ocular surface health status in primary open angle glaucoma (POAG) patients switching from topical application of...
The purpose of the present study was to assess the ocular surface health status in primary open angle glaucoma (POAG) patients switching from topical application of preserved latanoprost (LT) to preservative-free tafluprost (PFT) by tear proteomic monitoring. Tear fluid of POAG patients showing dry eye symptoms, using LT and switching to PFT as well as tear fluid of healthy controls has been examined. Tear proteome dynamics was monitored over 24 weeks in a first mass spectrometric explorative analysis in a small POAG patient cohort ( = 3). Longitudinal responses of candidate proteins as well as cytokines were comparatively analyzed by microarray in a larger cohort of POAG patients ( = 16) and healthy controls ( = 15). Clinical parameters including tear breakup time (TBUT) and basal test (BST) were recorded. Distinct post-switch level alterations could be documented in POAG tear proteins (> 1000). Cellular leakage proteins, dry eye related candidates and cytokines showed predominantly level diminishment in POAG patients and approximation to the tear protein level of healthy controls in response to PFT. Tear proteins like pyruvate kinase isozymes M1/M2 or galectin 7 displayed linear tear film level decline in POAG patients (R≥0.9; P < 0.05) distinctly converging the healthy level. Proteomic outcome fit well with improved clinical parameters, TBUT and BST. In conclusion, tear proteomic alterations indicated ocular surface recovery regarding epithelia leakage and inflammation recession. Together with improved clinical parameters the study output proposes beneficial effects of PFT glaucoma therapy.
PubMed: 27829990
DOI: No ID Found -
Translational Vision Science &... Aug 2020Lacritin is a tear glycoprotein with pro-tearing and pro-ocular surface homeostasis activities that is selectively deficient in most dry eye tears. Proteoforms include...
PURPOSE
Lacritin is a tear glycoprotein with pro-tearing and pro-ocular surface homeostasis activities that is selectively deficient in most dry eye tears. Proteoforms include an active monomer, inactive polymers, and a splice variant termed lacritin-c. Quantitation of the different proteoforms of tear lacritin may provide a diagnostic tool for ocular diseases. Here, we report the development of an immunoassay for the quantification of multiple lacritin proteoforms in human tear samples.
METHODS
Basal tears collected on Schirmer test strips with anesthesia were eluted by diffusion and centrifugation under optimized conditions. Tear protein concentrations were determined, and 2.56 µg of each sample was separated by SDS-PAGE followed by western blot analysis. Blots were challenged with anti-Pep Lac N-term antibodies. Detection was with fluorescent secondary antibodies visualized by the LI-COR Odyssey CLx imaging system and quantified with standard curves of recombinant lacritin.
RESULTS
The percent total lacritin (ng lacritin/100 ng total protein) ranged from 1.8% to 14.8%. Monomer, lacritin-c, and polymer proteoform percent total protein ranged from 1.1% to 6.3%, 0.3% to 5.4%, and 0.7% to 5.7%, respectively. Monomer lacritin was detected at concentrations of 6 to 176 µM, with lacritin-c and polymer proteoforms at 2 to 46 µM and 1 to 23 µM, respectively.
CONCLUSIONS
This assay greatly exceeds the power and sensitivity of our prior lacritin enzyme-linked immunosorbent assay that was not capable of distinguishing monomer from polymers and lacritin-c proteoforms.
TRANSLATIONAL RELEVANCE
A new method has been developed to quantitate multiple proteoforms of tear lacritin in preparation for analyses of samples from clinical trials.
Topics: Blotting, Western; Dry Eye Syndromes; Eye Proteins; Glycoproteins; Humans; Tears
PubMed: 32879769
DOI: 10.1167/tvst.9.9.13