OBJECTIVE: This study aims to address the issues surrounding the diagnosis of ocular rosacea and to evaluate the development of the patients’ condition after treatment, as well as to distinguish between healthy and diseased patients using a glycomic analysis of tears. METHODOLOGY: A prospective study was conducted to assess a total of 68 eyes in 34 patients over a six-week period. These patients were diagnosed with ocular rosacea based on subjective symptoms and clinical examination. The study monitored the development of objective and subjective values. The difference between patients with the pathology and healthy controls was established by means of analysis of glycans in tears. RESULTS: Skin lesions were diagnosed in 94% of patients with ocular rosacea, with the most commonly observed phenotype being erythematotelangiectatic (68.8%). The mean duration of symptoms was 29.3 months (range 0.5–126 months) with a median of 12 months. Throughout the study, an improvement in all monitored parameters was observed, including Meibomian gland dysfunction, bulbar conjunctival hyperemia, telangiectasia of the eyelid margin, anterior blepharitis, uneven and reddened eyelid margins, and corneal neovascularization. The study also observed improvements in subjective manifestations of the disease, such as foreign body sensation, burning, dryness, lachrymation, itching eyes, photophobia, and morning discomfort. The analysis of glycans in tears partially separated tear samples based on their origin, which allowed for the differentiation of patients with rosacea from healthy controls. In the first sample, the pathology was determined in a total of 63 eyes (98.4%) of 32 patients, with further samples showing a change in the glycomic profile of patients’ tears during treatment. CONCLUSION: The study demonstrated objective and subjective improvements in all the patients. Tear sampling and analysis could provide a means of timely diagnosis of ocular rosacea.
- Klíčová slova
- acne rosacea, ocular rosacea, dry eye syndrome, blepharitis, Meibomian gland dysfunction, rosacea diagnosis, glycomic analysis of tears,
- MeSH
- lidé MeSH
- oční nemoci * diagnóza MeSH
- polysacharidy terapeutické užití MeSH
- prospektivní studie MeSH
- rosacea * diagnóza farmakoterapie MeSH
- slzy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- polysacharidy MeSH
The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms.
- Klíčová slova
- cell line, dry eye, epithelial cells, immortalized, lacrimal gland, tear secretion, tears,
- MeSH
- buněčné linie MeSH
- lidé MeSH
- slzné ústrojí * metabolismus MeSH
- slzy metabolismus MeSH
- syndromy suchého oka * metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Glaucoma is a leading cause of blindness worldwide, with elevated intraocular pressure being a major risk factor for its development and progression. First-line treatment for glaucoma relies on the administration of prostaglandin analogs, with latanoprost being the most widely used. However, before latanoprost reaches the cornea, it must pass through the tear film and tear film lipid layer (TFLL) on the ocular surface. Given the significant lipophilicity of latanoprost, we hypothesize that TFLL could, to a certain extent, act as a reservoir for latanoprost, releasing it on longer time scales, apart from the fraction being directly delivered to the cornea in a post-instillation mechanism. We investigated this possibility by studying latanoprost behavior in acellular in vitro TFLL models. Furthermore, we employed in silico molecular dynamics simulations to rationalize the experimental results and obtain molecular-level insight into the latanoprost-TFLL interactions. Our experiments demonstrated that latanoprost indeed accumulates in the TFLL models, and our simulations explain the basis of the accumulation mechanism. These results support the hypothesis that TFLL can serve as a reservoir for latanoprost, facilitating its prolonged release. This finding could have significant implications for optimizing glaucoma treatment, especially in the development of new drug delivery systems targeting the TFLL.
- Klíčová slova
- Glaucoma, Latanoprost, Ophthalmology, Tear film, Tear film lipid layer, Topical delivery,
- MeSH
- antihypertenziva terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- latanoprost terapeutické užití MeSH
- lidé MeSH
- nitrooční tlak MeSH
- počítačová simulace MeSH
- rohovka MeSH
- slzy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antihypertenziva MeSH
- latanoprost MeSH
PURPOSE: To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls. METHODS: Observational case-control study. Tear samples were collected by 5 µl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF. RESULTS: Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals. CONCLUSION: This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
- Klíčová slova
- Cytokines, Glaucoma, Inflammation, Ocular hypertension, Tears,
- MeSH
- antihypertenziva terapeutické užití MeSH
- cytokiny metabolismus MeSH
- glaukom s otevřeným úhlem * MeSH
- glaukom * farmakoterapie MeSH
- interleukin-10 metabolismus MeSH
- interleukin-4 metabolismus MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze * MeSH
- oční roztoky MeSH
- slzy metabolismus MeSH
- studie případů a kontrol MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- antihypertenziva MeSH
- cytokiny MeSH
- interleukin-10 MeSH
- interleukin-4 MeSH
- oční roztoky MeSH
- vaskulární endoteliální růstový faktor A MeSH
Benzalkonium chloride (BAK) compounds are commonly used in topical ophthalmic products as preservatives and stabilizers. BAK mixtures containing several compounds with different alkyl chain lengths are typically used. However, in chronic eye conditions, such as dry eye disease and glaucoma, the accumulation of adverse effects of BAKs was observed. Hence, preservative-free eye drops formulations are preferred. On the other hand, selected long-chain BAKs, particularly cetalkonium chloride, exhibit therapeutic functions, promoting epithelium wound healing and tear film stability. Nevertheless, the mechanism of BAKs influence on the tear film is not fully understood. By employing in vitro experimental and in silico simulation techniques, we elucidate the action of BAKs and demonstrate that long-chain BAKs accumulate in the lipid layer of the tear film model, stabilizing it in a concentration-dependent fashion. In contrast, short-chain BAKs interacting with the lipid layer compromise the tear film model stability. These findings are relevant for topical ophthalmic drug formulation and delivery in the context of selecting proper BAK species and understanding the dose dependency for tear film stability.
- Klíčová slova
- Benzalkonium chloride, Lipid films, Molecular dynamics, Tear film, Tear film lipid layer, Topical ophthalmic formulations,
- MeSH
- benzalkoniové sloučeniny škodlivé účinky MeSH
- konzervační prostředky farmaceutické * farmakologie MeSH
- lidé MeSH
- lipidy farmakologie MeSH
- oční roztoky MeSH
- slzy MeSH
- syndromy suchého oka * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzalkoniové sloučeniny MeSH
- konzervační prostředky farmaceutické * MeSH
- lipidy MeSH
- oční roztoky MeSH
Tear production is an important factor in maintaining proper function of the cornea and conjunctiva. The purpose of this study was to determine the effects of bolus followed by infusion of fentanyl, lidocaine, and ketamine on tear production as measured by the Schirmer I Tear Test (STT-I) in dogs. A prospective, randomized, "double-blind" study was performed. A total of 55 healthy conscious client-owned dogs were included in the study. Dogs were randomly allocated to one of four groups and given intravenous fentanyl 0.005 mg kg-1 followed by 0.005 mg kg-1 hour-1 (FEN-group), ketamine 0.6 mg kg-1 followed by 0.6 mg kg-1 hour-1 (KET-group), lidocaine 1 mg kg-1 followed by 1 mg kg-1 hour-1 (LID-group), or saline 0.3 mL kg-1 followed by 2 mL kg-1 hour-1 (SAL-group). The STT-I was performed prior to (baseline) and again 30 minutes (T30) after initiation of drug administration. Data were expressed as the median (minimum - maximum) and analyzed by Wilcoxon and Steel-Dwass tests (P < .05). The STT-I values increased little but were statistically significant in the KET-group from 18 (14-23) to 19 (14-25) (P = .039) and in the LID-group from 21 (14-25) to 20 (17-29) (P = .027). At 30 minutes, STT-I values were significantly higher in LID-group 20 (17-29) than in FEN-group 18 (12-22) (P = .006). Fentanyl, ketamine, and lidocaine administered at the studied doses as a bolus and then followed by an infusion within 30 minutes in healthy conscious dogs demonstrated a clinically insignificant effect on tear production as measured by STT-I.
- Klíčová slova
- fentanyl, ketamine, lidocaine, tear production,
- MeSH
- fentanyl farmakologie MeSH
- ketamin * farmakologie MeSH
- lidokain farmakologie MeSH
- prospektivní studie MeSH
- psi MeSH
- slzy MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie veterinární MeSH
- Názvy látek
- fentanyl MeSH
- ketamin * MeSH
- lidokain MeSH
OBJECTIVE: The aim of this systematic review is to summarize outcomes of studies focused on the effects of opioids, injectable sedative and anaesthetic drugs and inhalant anaesthetics on tear production in dogs. This manuscript complements the systematic review describing the effect of anaesthetics on intraocular pressure in dogs (Pierce-Tomlin et al. 2020). Databases used A detailed search of scientific references has been performed. PubMed, Web of Science, Science Direct and Google Scholar databases were used to search for sources using free text terms 'Dog' or 'Canine', 'Anaesthesia' or 'Anaesthetic' or 'Sedative' or 'Opioid' or the name of used opioids, sedative and anaesthetic drugs and 'Tear' or 'Schirmer' or 'Lacrimation'. The time frame searched was from 1960 to October 2021. Any published manuscripts that were concerned with sedative or anaesthetic drugs administered systemically in the dog and tear production were evaluated. CONCLUSIONS: Low doses of α2-adrenoceptor agonists, neuroleptics, benzodiazepines, opioids, propofol or alfaxalone administered alone have no clinically significant effect on aqueous tear production in healthy dogs measured by the Schirmer tear test I (STT-I). Intramuscular injection of ketamine increases STT-I values. Higher doses of α2-adrenoceptor agonists and combinations of anaesthetics, including inhaled anaesthetics, always clinically significantly decrease tear production.
- Klíčová slova
- Schirmer tear test, anaesthesia, dog, tear production,
- MeSH
- adrenergní receptory MeSH
- anestetika * farmakologie MeSH
- hypnotika a sedativa farmakologie MeSH
- propofol * farmakologie MeSH
- psi MeSH
- slzy MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- adrenergní receptory MeSH
- anestetika * MeSH
- hypnotika a sedativa MeSH
- propofol * MeSH
The preocular tear film is critically important for maintaining healthy ocular surface. In lagophthalmos, increased evaporation and tear film instability can occur. The level of tear matrix metalloproteinase 9 (MMP-9) is considered as a possible marker of ocular surface damage and inflammation. The aim of this study was to evaluate the possible usefulness of measuring tear film levels of MMP-9 in patients with lagophthalmos. Sixteen adult patients with unilateral lagophthalmos due to cerebellopontine angle mass surgery were included. Basic clinical examination including tear film osmolarity, degree of lagophthalmos, ocular surface sensitivity testing, corneal fluorescein staining, and tear break-up time (TBUT) were performed. Furthermore, tear MMP-9 quantification was performed and the values from lagophthalmic and contralateral healthy eye were compared. Possible correlations between tear MMP-9 levels and other parameters were analyzed. The Oxford score was higher in lagophthalmic eyes in comparison to healthy eyes. TBUT and corneal sensitivity were lower in lagophthalmic eyes. There was no difference in osmolarity between the two groups. Tear MMP-9 values were higher in lagophthalmic eyes. A higher MMP-9 value was associated with an increase in ocular surface fluorescein staining and a decrease of TBUT in lagophthalmic eyes. Tear MMP-9 may be used for monitoring ocular surface damage, contribute to early detection of inflammation progression and facilitate treatment adjustments.
- MeSH
- dospělí MeSH
- fluorescein MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 MeSH
- nemoci očních víček * MeSH
- osmolární koncentrace MeSH
- poranění oka * MeSH
- slzy MeSH
- syndromy suchého oka * diagnóza MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluorescein MeSH
- matrixová metaloproteinasa 9 MeSH
OBJECTIVE: To investigate the physiological profile of pro-inflammatory and anti-inflammatory cytokines in tears produced by epithelial cells under the effect of endogenous and exogenous biological factors. Knowing the physiological cytokine profile in tears with its biological characteristics including sex- and age-specific effects is fundamental when tears are analyzed for diagnostic or prognostic purposes in eye diseases. METHODS: Tear samples were collected from right eye of 45 healthy volunteers (24 males, 21 females) by 5 μl microcapillary tube. Cytokines interleukin 1β, interleukin 10, interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor were quantified by multiplex Bio-Plex system. RESULTS: The production of macrophage migration inhibitory factor cytokine by epithelial cells on the ocular surface is higher in males compared to females (p = 0.05); actually, most of female tear samples present with undetectable macrophage migration inhibitory factor levels. Our results show the negative correlations between the age and concentrations of interleukin 4 (p < 0.01) and interferon gamma (p < 0.01) in tears, respectively, and positive associations of vascular endothelial growth factor levels with the age above 45 years (p < 0.05). CONCLUSIONS: Data in this study indicate that age and sex may affect the physiological levels of cytokines in tears. Consequently, the impacts of biological factors need to be recognized and taken into consideration before the levels of cytokines in patients' tears are analyzed for medical reasons. Concentrations of interleukin 1β and interleukin 10 cytokines, however, are very low in healthy tears and do not seem to be influenced by studied biological factors; therefore, they meet the requirements for analytes suitable for medical diagnostic and prognostic purposes.
- Klíčová slova
- Tears, age, interferon gamma, interleukin 10, interleukin 1β, interleukin 4, macrophage migration inhibitory factor, sex, vascular endothelial growth factor,
- MeSH
- inhibiční faktory migrace makrofágů * metabolismus MeSH
- interferon gama * metabolismus MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta * metabolismus MeSH
- interleukin-4 * metabolismus MeSH
- lidé MeSH
- sexuální faktory MeSH
- slzy * metabolismus MeSH
- vaskulární endoteliální růstový faktor A * metabolismus MeSH
- věkové faktory MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inhibiční faktory migrace makrofágů * MeSH
- interferon gama * MeSH
- interleukin-10 MeSH
- interleukin-1beta * MeSH
- interleukin-4 * MeSH
- vaskulární endoteliální růstový faktor A * MeSH
The ocular surface is in constant interaction with the environment and with numerous pathogens. Therefore, complex mechanisms such as a stable tear film and local immune defense mechanisms are required to protect the eye. This study describes the detection, characterization, and putative role of surfactant protein G (SP-G/SFTA2) with respect to wound healing and surface activity. Bioinformatic, biochemical, and immunological methods were combined to elucidate the role of SP-G in tear film. The results show the presence of SP-G in ocular surface tissues and tear film (TF). Increased expression of SP-G was demonstrated in TF of patients with dry eye disease (DED). Addition of recombinant SP-G in combination with lipids led to an accelerated wound healing of human corneal cells as well as to a reduction of TF surface tension. Molecular modeling of TF suggest that SP-G may regulate tear film surface tension and improve its stability through specific interactions with lipids components of the tear film. In conclusion, SP-G is an ocular surface protein with putative wound healing properties that can also reduce the surface tension of the tear film.
- Klíčová slova
- dry eye, ocular surface, surface tension, surfactant protein, tear film,
- MeSH
- lidé MeSH
- lipidy analýza MeSH
- povrchové napětí MeSH
- rohovka metabolismus MeSH
- slzy * metabolismus MeSH
- syndromy suchého oka * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidy MeSH