scholarly journals Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 344
Author(s):  
Dmitry V. Chistyakov ◽  
Olga S. Gancharova ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
...  

Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways).

2021 ◽  
pp. 6-11
Author(s):  
K.N. Odinaeva ◽  
◽  
N.S. Al Khateeb ◽  
M.A. Frolov ◽  
◽  
...  

Purpose. To determine and study the features of the development of dry eye syndrome (DES) in gout, depending on urate-lowering therapy, the duration of the gout disease and the concentration of uric acid in the tear. Material and methods. The study involved 149 male patients (261 eyes) aged 35 to 75 years (mean age 60.63 ± 11.00 years). Among them, 110 people (202 eyes) with an established diagnosis: "Cataract with concomitant gout disease" and 39 people (59 eyes) with cataracts without clinical and laboratory signs of gout. All patients underwent both standard ophthalmological examinations and special ones. The concentration of uric acid in tears was determined by high performance liquid chromatography (HPLC). The diagnosis of gout was confirmed according to the criteria recommended by ACR / EULAR (2016). Results. In patients with gout who do not take a urate-lowering drug, DES occurs more often (82.1%) than in patients without gout (23.1%). With an increase in the concentration of uric acid in the tear, there is a high tendency to a shortening of the tear film rupture time (strong correlation coefficient r=-0.51, p<0.001) and to a decrease in tear production (Schirmer I test) (strong correlation coefficient r=-0.59, p<0.001). Conclusion. The data obtained indicate clear changes in the functional parameters of total tear production (Schirmer I's test) and the stability of the pre-corneal tear film (Norn's test) in patients with gout. This can be considered as a fact of the predisposition of this category of patients to the development of DES. A strong dependence of changes in tear production and HRVP on the concentration of uric acid in the tear was established. There is an obvious need for additional examination of this category of patients and an adequate choice of therapy, as well as the timely appointment of "artificial tear" drugs. Key words: dry eye syndrome, uric acid, gout.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3245
Author(s):  
Sung-Chul Hong ◽  
Jung-Heun Ha ◽  
Jennifer K. Lee ◽  
Sang Hoon Jung ◽  
Jin-Chul Kim

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.


2005 ◽  
Vol 6 (3) ◽  
pp. 185-196
Author(s):  
Lorenzo Pradelli ◽  
Letizia Vacchini

BACKGROUND: The dry eye sindrome refers to a group of disorders of the tear film due to reduced tear production or excessive tear evaporation that is associated with symptoms of ocular discomfort and may cause disease of the ocular surface. Dry eye syndrome varies in severity, duration and etiology. The cornerstone of dry eye syndrome therapies includes the intraocular gel or ophthalmic solutions instillation, reaching correct artificial lubrication. Molecules that can produce a stable lubricating film are the carbomers. METHODS: In the first step of our work we reviewed the data from literature reporting about carbomers’ characteristics in respect to other lacrimal substitutes. Then, a pharmacoeconomical analysis has been performed on ophtalmic gels derived from carbomers 974P and PVA. RESULTS: Dry eye sindrome, if not adequately treated, determines a deterioration of the patient’s quality of life, other than high secondary costs. CONCLUSION: The high therapeutical index of carbomers 974P and PVA-based gels, in addition to the their limited cost (totally free for Sjögren patients in Italy), suggests that this product is characterized by one of the best benefits-to-costs ratios in the treatment of dry eye sindrome.


2019 ◽  
Vol 16 (1) ◽  
pp. 70-75
Author(s):  
L. I. Uchakova ◽  
S. V. Balalin ◽  
V. L. Zagrebin

The aim is to evaluate the effectiveness of Stillavit in the treatment of dry eye syndrome (DES) and its effect on the density of conjunctival goblet cells and the functional parameters of tear production. Methods. There were analyzed treatment results of 18 patients (36 eyes) with DES at the age of 48 to 80 years (average 60.6 ± 1.3 years) including 17 women and 1 male before and after 1 and 3 months after Stillavit prescription. In all patients in addition to a standard ophthalmological examination the results of Schirmer I, Norn, as well as the LIPCOF test were evaluated and the density of conjunctival goblet cells was examined. Results. After 1 and 3 months there was a significant improvement in the results of the Norn test: from 5.17 ± 0.22 seconds to 7.18 ± 0.17 seconds which indicated an increase in the stability of the tear film. After 3 months there was a significant increase in the density of conjunctival goblet cells, improvement in the Schirmer sample: from 9.26 ± 0.89 to 11.7 ± 0.6 mm (t = 2.28, p < 0.05) and LIPCOF test (t = 2.18, p < 0.05) which indicated an increase in tear production and a significant decrease in the inflammatory process and edema of the conjunctiva. Conclusion. Treatment of DES with the use of Stillavit leads after 3 months to a significant increase in the density of conjunctival goblet cells, increases tear production and stability of the tear film.


2020 ◽  
Author(s):  
Hui DU ◽  
Yifei RAO ◽  
Ronghua LIU ◽  
Kesui DENG ◽  
Yongmei GUAN ◽  
...  

Abstract Background: Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear.Methods: In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. ITRAQ markers, combined with LC-MS/MS proteomics technology and the UHPLC/ Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia.Results: A total of 137 differentially expressed proteins were identified, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses and regulation of acute inflammatory responses. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. Analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, alpha-linolenic acid, linoleic acid and arachidonic acid metabolism, suggesting that regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered a potential biomarker of dyslipidemia. Conclusions: Combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker.The information provided in this study may provide new insights into the pathogenesis of dyslipidemia and related diseases, as well as potential intervention targets.


2020 ◽  
Vol 17 (3) ◽  
pp. 519-526
Author(s):  
A. V. Kuroyedov ◽  
P. Ch. Zavadski ◽  
A. Yu. Brezhnev ◽  
V. V. Gorodnichii ◽  
I. R. Gazizova ◽  
...  

Purpose. To study the influence of personal protective equipment (PPE) of the respiratory and visual systems on the development and progression of dry eye syndrome (DES) and its relationship with other risk factors for medical workers.Patients and methods. The data of 243 people (male — 22.2 %, female — 77.8 %) were analyzed as part of a multi-center analytical scientific one-step study. Total tear production (Schirmer I test) was studied at the beginning and the end of the working day in persons used PPE of respiratory system (disposable medical face mask, gauze masks or different types of respirators), as well as PPE of the eyes (protective half-closed/closed glasses or protective screens). Risk factors for the development and progression of DES were registered (age, smoking, systemic hormones intake, soft contact lenses), as well as the use of artificial tears.Results. A decrease in the Schirmer I test score at the end of a 7–8 hour work shift was found by an average of 3 mm (from 13 (9; 16) mm to 10 (6; 15) mm, p < 0.001). Statistically significant changes were typical mainly for medical personnel (p < 0.001) with the maximum severity in persons working in outpatient sector. The presence of at least one DES risk factor was found in 30.5 % of patients, two factors — in 3.0 %, and three or more — in 7.0 %. There was no influence of risk factors on the degree of changes in total tear production. Reduced tear production is typical for some PPE of respiratory system (disposable masks and respirators) and the eye (screens and half-closed glasses) (p < 0.001). In people who do not use PPE of the eye, significant changes were detected only in the presence of risk factors.Conclusion. The negative influence of various PPE of the respiratory system and eye on the total tear production was established. The decrease in the results of the Schirmer I test by the end of the working day was 20–25 % of the basic level, regardless of the presence of traditional risk factors for DES. The severity of changes depended on the type of PPE used. The data obtained are particularly relevant during the new COVID-19 coronavirus pandemic and justify the need to establish specific prophylactic measures. One of the possible methods is the preventive use of artificial tears. 


2020 ◽  
Vol 17 (1) ◽  
pp. 124-132
Author(s):  
I. A. Gndoyan ◽  
A. V. Petrayevsky

Purpose: evaluation of the efficacy of the drug Tealose® in the therapy of cornea inflammatory diseases consequences such as dry eye syndrome.Patients and methods: 34 patients (34 eyes) with dry eye syndrome after inflammatory diseases of the cornea, aged 28–56 years old were included in the study. Two clinical groups were formed: observation group — 20 subjects (20 eye) and comparison group — 14 subjects (14 eyes). The dynamics of such indicators were estimated under therapy: visual acuity with maximal correction, corneal epithelium entity according fluoresceine dye test, tear production according Schirmer and Norn tests, the grade of dry eye syndrome severity according index of OSDI — Questionnarie. The patients in observation group in addition to the basic therapy, which included instillation antiseptics и 4 % taurine solution, were treated with 3 % solution of tregalose (Tealose®, “Laboratuar Thea”, France) by such mode: using of 4 times daily instillations during 1 month, 1 month break, than continuation of the same regimen instillations during 1 month was performed. The patients in comparison group in addition to the same basic therapy were treated with Visomitin® (“Mitotech”, Russia) by the mode, which was used for tregalose.Results. The improvement of cornea’s epithelization (p < 0,05), increasing of visual acuity with maximal correction (p < 0,05), improvement of tear production (p < 0,05), as well as the OSDI-index (p < 0,05) were revealed in the patients of the observation group. In the patients of the comparison group positive dynamics of these indicators was insignificant and unreliable.Conclusions. Using of 3 % tregalose solution in patients with consequences of inflammatory diseases of the cornea — keratitis leads to effective treatment of “dry eye” syndrome, reduces the severity of epithelization disorders and tendency to scarring in the corneal tissue.


The Eye ◽  
2019 ◽  
Vol 127 (2019-3) ◽  
pp. 28-33
Author(s):  
Alexander Kravchenko ◽  
Olga Shilova

Purpose: Comparison of dry eye syndrome stages with intensity of changes in peripheral retina in patients undergoing medical therapy. Material and methods. The clinical study involved 94 patients with mild and moderate dry eye syndrome (DES). Group 1 and Group 2 were both comprised of 25 patients; group 3 was comprised of 44 patients. The observation period was 6 months. Parameters of the anterior eye surface and intensity of changes in the peripheral retina were subjected to evaluation and comparison. Results. The study has shown, that the radius of the tear meniscus, surface tension coefficient and the number of areas stained with fluorescein significantly correlate with the probability of changes in the peripheral retina. The interrelation between the probable formation of changes in the peripheral parts of the retina and the indicators of tear production was revealed in all patients. After 3 months the performed treatment led to the disappearance of the initial correlation between the factors: on visits 3 and 4 logit-models appeared to be unreliable, that meant the absence of interrelation between the probability of formation of changes in the peripheral retina and indicators characterizing the condition of the anterior ocular surface or tear production. Conclusion. The correlation between changes in the peripheral parts of the retina and tear production was described.


2017 ◽  
Vol 10 (4) ◽  
pp. 13-17
Author(s):  
Natalya Yu Beldovskaya ◽  
Sergey A Karpichenko ◽  
Svetlana V Baranskaya ◽  
Artemiy A Karpov

Introduction. Radioactive iodine therapy after thyroidectomy is the standard of differentiated thyroid cancer treatment in the modern world. Main dose-dependent side effects described in the literature include: sialadenitis, xerostomia, taste and/or odor loss, swelling of surrounding tissues. Ophthalmic complications are rarely reported. Aim. To assess the lacrimal system condition in patients after radioactive iodine therapy for thyroid cancer. Material and methods. The study included 17 patients (34 eyes). There were female patients aged 19 to 43 years (mean age was 31 years) who underwent a course of radioactive iodine therapy for thyroid cancer. All of them complained of periodic or constant tearing in the period from 2 months to 1 year after therapy course. In four patients, there was a permanent or periodic mucopurulent discharge when pressing on the lacrimal sac area. All patients underwent a standard ophthalmological examination, including visual acuity testing, anterior segment biomicroscopy, ophthalmoscopy, and tear production tests. Dye disappearance test, Jones I and II tests, lacrimal pathways irrigation, and, if necessary, cone-ray computer tomography with preliminary lacrimal pathways contrasting were performed to evaluate the tear outflow abnormalities. Results. Tear production disorders were detected in 20 eyes (58.8%) (among them, moderate dry eye syndrome was diagnosed in 3 cases); tear outflow pathology was revealed in 14 eyes (41.2%) (namely naso-lacrimal duct obstruction and stenosis, and chronic purulent dacryocystitis). For patients with tear production pathology artificial tears were prescribed, and endoscopic endonasal dacryocystorhinostomy was performed in cases of tear outflow disturbances. Conclusion. The use of radioactive iodine in doses exceeding 80 mCi leads to the development of lacrimal system pathology: dry eye syndrome of various severity, and tear outflow disorders. Lacrimal system pathology significantly worsens the patient's quality of life, and the prophylaxis of these diseases before the radioactive iodine therapy course remains the imminent key problem. (For citation: Beldovskaya NYu, Karpishchenko SA, Baranskaya SV, Karpov AA. Lacrimal system pathology in patients with ­malignant thyroid tumors after radioactive iodine therapy, and its correction methods. ­Ophthalmology Journal. 2017;10(4):13-17. doi: 10.17816/OV10413-17).


Sign in / Sign up

Export Citation Format

Share Document