A Novel Selective 11β-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye Syndrome

Dry eye syndrome is the most common eye disease and it is caused by various reasons. As the balance of the tear film that protects the eyes is broken due to various causes, it becomes impossible to properly protect the eyes. In this study, the protective effects and underlying mechanisms of topical (E)-4-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)adamantan-1-carboxamide (KR-67607), a novel selective 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor, were investigated in benzalkonium chloride (BAC)-induced dry eye syndrome. BAC-treated rat eyes induced significant increases in ocular surface damage, decreased corneal thickness, corneal basement membrane destruction in the conjunctival epithelium, and expression of pro-inflammatory cytokines tumor necrosis factor-α and 11β-HSD1. These effects of BAC were reversed by topical KR-67607 treatment. Furthermore, KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. Taken together, a novel selective 11β-HSD1 inhibitor can prevent BAC-induced dry eye syndrome by inhibiting pro-inflammatory cytokine and reactive oxygen species expression via the inhibition of both 11β-HSD1 activity and expression.

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Interleukin-6 and Tumor Necrosis Factor-α Levels in Tears of Patients With Dry Eye Syndrome

Cornea ◽

10.1097/ico.0b013e31803dcda2 ◽

2007 ◽

Vol 26 (4) ◽

pp. 431-437 ◽

Cited By ~ 141

Author(s):

Kyung-Chul Yoon ◽

In-Young Jeong ◽

Yeoung-Geol Park ◽

Sung-Yeul Yang

Keyword(s):

Tumor Necrosis Factor ◽

Dry Eye ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Dry Eye Syndrome ◽

Factor Α ◽

Necrosis Factor

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Kaempferol Attenuates LPS-Induced Striatum Injury in Mice Involving Anti-Neuroinflammation, Maintaining BBB Integrity, and Down-Regulating the HMGB1/TLR4 Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms20030491 ◽

2019 ◽

Vol 20 (3) ◽

pp. 491 ◽

Cited By ~ 17

Author(s):

Ying-Lin Yang ◽

Xiao Cheng ◽

Wei-Han Li ◽

Man Liu ◽

Yue-Hua Wang ◽

...

Keyword(s):

Protective Effects ◽

Neuroprotective Effects ◽

Chemotactic Protein ◽

Tnf Α ◽

Factor Α ◽

Cell Adhesion Molecule 1 ◽

Neuron Injury ◽

Intercellular Cell Adhesion Molecule ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Neuroinflammation has been demonstrated to be linked with Parkinson’s disease (PD), Alzheimer’s disease, and cerebral ischemia. Our previous investigation had identified that kaempferol (KAE) exerted protective effects on cortex neuron injured by LPS. In this study, the effects and possible mechanism of KAE on striatal dopaminergic neurons induced by LPS in mice were further investigated. The results showed that KAE improved striatal neuron injury, and increased the levels of tyrosine hydroxylase (TH) and postsynaptic density protein 95 (PSD95) in the striatum of mice. In addition, KAE inhibited the production of pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), reduced the level of monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2) in the striatum tissues. Furthermore, KAE protected blood-brain barrier (BBB) integrity and suppressed the activation of the HMGB1/TLR4 inflammatory pathway induced by LPS in striatum tissues of mice. In conclusion, these results suggest that KAE may have neuroprotective effects against striatum injury that is induced by LPS and the possible mechanisms are involved in anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1/TLR4 pathway.

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ABIN1 alleviates inflammatory responses and colitis via facilitating A20 activity

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622320944782 ◽

2020 ◽

Vol 11 ◽

pp. 204062232094478

Author(s):

Tian Pu ◽

Wenzheng Liu ◽

Yijun Wu ◽

Ye Zhao

Keyword(s):

Tumor Necrosis Factor ◽

Inflammatory Cytokines ◽

Tumor Necrosis ◽

Inflammatory Responses ◽

Myeloid Cell ◽

Protein Levels ◽

Underlying Mechanisms ◽

Factor Α ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Background: Macrophages-mediated inflammation is involved in the progress of colitis. The present study aims to explore the roles of A20-binding inhibitor of NF-κB (ABIN1) in the macrophages and its underlying mechanisms. Methods: ABIN1 myeloid cell-conditional transgenic mice were established and genotyped by PCR and immunoblotting assays. Tumor necrosis factor (TNF)-α was applied to pre-treat bone marrow-derived macrophages (BMDMs) in the presence of lipopolysaccharide. The mRNA and protein levels of pro-inflammatory cytokines were determined by qRT-PCR and ELISA, respectively. Dextran sulfate sodium (DSS)-induced colitis was established to determine the effects of ABIN1 on the survival time, body weight, colon length, and colon histopathological changes. Western blotting was applied to determine the expressions of signaling proteins. Results: ABIN1 overexpression did not affect cell populations of macrophages and neutrophils in mice. Its overexpression reduced the productions of pro-inflammatory cytokines in BMDMs and ameliorated survival rate and colitis symptoms in the DSS-induced mouse model. The underlying mechanisms revealed that ABIN1 impaired macrophages-mediated inflammatory responses, in part by regulating the NF-κB signal pathway, and its ameliorated effects on the symptoms of DSS-induced colitis were associated with A20/tumor necrosis factor α-induced protein 3 (TNFAIP3). Conclusion: ABIN1 attenuated inflammatory responses and colitis by regulating A20/TNFAIP3 activities.

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PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production

Cell Death and Differentiation ◽

10.1038/s41418-021-00780-5 ◽

2021 ◽

Author(s):

Yan Liang ◽

Xiaoli Sun ◽

Mingjie Wang ◽

Qingmiao Lu ◽

Mengru Gu ◽

...

Keyword(s):

Cell Death ◽

Tubular Cell ◽

Kidney Fibrosis ◽

Tubular Cells ◽

Ureter Obstruction ◽

Underlying Mechanisms ◽

Factor Α ◽

Rap1 Activation ◽

Necrosis Factor ◽

Macrophage Accumulation

AbstractMacrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα−/− macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

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Corneal topography and classical test in the diagnosis of dry eye syndrome in patients with myopia and myopic astigmatism before keratorefractive surgery

Modern technologies in ophtalmology ◽

10.25276/2312-4911-2021-1-39-43 ◽

2021 ◽

pp. 39-43

Author(s):

Y.V. Kutuzova ◽

◽

I.V. Dutchin ◽

E.L. Sorokin ◽

◽

...

Keyword(s):

Dry Eye ◽

Tear Film ◽

Risk Groups ◽

Corneal Topography ◽

Dry Eye Syndrome ◽

Film Rupture ◽

Keratorefractive Surgery ◽

The Stability ◽

High Degree ◽

Myopic Astigmatism

Purpose.To conduct a comparative analysis of the effectiveness of assessing the stability of the tear film using corneotopography and the classic Norn test in patients with myopia and myopic astigmatism before keratorefractive surgery. Material and methods. The study included 26 patients planned for keratorefractive surgery for myopia and myopic astigmatism, aged 18 to 47 years. 7 people there was a mild degree of myopia, in 14 people – medium degree, in 5 people – high degree. The average degree of corneal astigmatism was 2.25 diopters. The stability of the pre-corneal tear film was assessed using computed keratotopography and Norn's test – the tear film rupture time (TFRT) was deter- mined. A standard questionnaire was also used to assess the severity of symptoms of dry eye syndrome. A comparison was made of the indicators of the stability of the tear film obtained by the methods of corneotopography and the Norn's test, with their subsequent comparison with the data of the questionnaire. Results. In 17 patients (65.4%), the TFRT index corresponded to the age norm. In the remaining 9 people (34.6%), indicators of stability of the tear film were reduced both by corneotopography (12±4 sec) and by Norn's test (13.5±4.5 sec), and there were also subjective signs of dry eye syndrome according to data questionnaire. The data turned out to be comparable. Conclusions. 1. Among the total population of patients, 34.6% were persons with impaired tear film stability and subjective manifestations of dry eye syndrome. 2. Assessment of the stability of the tear film, determined using the method of corneal topography, showed a high degree of comparability with the results of Norn's test. A significant advantage of the keratotopography method is its non-invasiveness. 3. It is necessary to pay attention to the condition of the ocular surface and identify risk groups to avoid chronicity or aggravation of existing disorders. Key words: dry eye syndrome, tear film, keratotopography, Norn's test.

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«Dry eye» syndrome and primary glaucoma: possibilities of treatment

Reflection ◽

10.25276/2686-6986-2020-1-42-44 ◽

2020 ◽

Vol 10 (1) ◽

pp. 42-44

Author(s):

L.I. Solovyova ◽

◽

T.V. Gavrilova ◽

F.G. Mugumova ◽

◽

...

Keyword(s):

Dry Eye ◽

Open Angle Glaucoma ◽

Tear Film ◽

Dry Eye Syndrome ◽

Rupture Time ◽

Eye Drops ◽

Film Rupture ◽

Good Tolerability ◽

Primary Glaucoma ◽

The Stability

The article presents the results of Ocuhyl C using in the treatment of «dry eye syndrome» (DES) in 47 eyes of 26 patients with different stages of compensated primary open-angle glaucoma. Experience of instillation of hypotensive eye drops with preservatives was from 1 year to 35 years. Assessment of subjective signs of DES was performed by questioning. Functional tests were performed (for the stability of the precorneal tear film –Norn test, for the level of total tear production –Shirmer test). Examinations were carried out at the first examination before prescribing the drug, then after 4 and 8 weeks of its use. All the patients noted good tolerability of the drug, no side effects. Indicators characterizing the feeling of a foreign body, dryness and redness of the eyes have significantly decreased. Precorneal tear film rupture time has significantly increased. Ocuhyl C can be recommended for clinical use. Key words: primary glaucoma; “dry eye” syndrome; tear forming; tear film rupture time; Ocuhyl C.

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PENGARUH EMISI DEBU SEMEN TERHADAP STATUS TEAR FILM MASYARAKAT DI SEKITAR PABRIK PT. SEMEN PADANG

Jurnal Kesehatan Andalas ◽

10.25077/jka.v6i3.753 ◽

2018 ◽

Vol 6 (3) ◽

pp. 654

Author(s):

Muhammad Syauqie ◽

Ardizal Rahman ◽

Getry Sukmawati

Keyword(s):

Dry Eye ◽

Tear Film ◽

Cross Sectional Study ◽

Dry Eye Syndrome ◽

Sectional Study ◽

Cross Sectional ◽

Break Up

Permukaan okular rentan terhadap efek iritatif dari debu semen tersebut karena epitel konyungtiva dan kornea hanya dilapisi oleh lapisan tipis tear film. Paparan debu semen jangka panjang menyebabkan terjadinya inflamasi subklinis kronik yang dapat mempengaruhi transdiferensiasi epitel konyungtiva dan densitas sel goblet yang kemudian dapat menyebabkan timbulnya gejala dry eye syndrome. Tujuan penelitian ini adalah menilai status tear film pada masyarakat yang terpapar emisi debu semen dibandingkan dengan masyarakat yang tidak terpapar. Penelitian ini berupa analytic cross sectional study pada dua populasi yaitu kelompok terpapar dan tidak terpapar emisi debu pabrik semen. Semua sampel penelitian dari dua populasi menjalani pemeriksaan pH tear film, Schirmer, Ferning dan Tear Break Up Time (TBUT). Hasil studi mendapatkan peningkatan nilai pH tear film yang bermakna pada penduduk di kelompok terpapar dengan p=0.001. Terdapat juga penurunan kualitas Ferning yang bermakna pada penduduk di kelompok terpapar yang didominasi tipe III dengan p=0.005 dan 0.029. Sedangkan hasil pemeriksaan Schirmer dan TBUT masih dalam batas normal dan tidak terdapat perbedaan yang bermakna antara kedua kelompok. Simpulan studi ini ialah erdapat peningkatan rerata nilai pH tear film dan penurunan kualitas lapisan musin tear film yang bermakna pada masyarakat yang terpapar emisi debu semen namun tidak didapatkan peningkatan kejadian dry eye yang bermakna.

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Gpr125 identifies myoepithelial progenitors at tips of lacrimal ducts and is essential for tear film

10.1101/2020.09.15.296749 ◽

2020 ◽

Author(s):

Elena Spina ◽

Rebecca Handlin ◽

Julia Simundza ◽

Angela Incassati ◽

Muneeb Faiq ◽

...

Keyword(s):

Dry Eye ◽

Essential Role ◽

Tear Film ◽

Lineage Tracing ◽

Dry Eye Syndrome ◽

Planar Polarity ◽

Inflammatory Infiltration ◽

Discrete Population ◽

Signaling Domains ◽

G Protein Coupled

AbstractGpr125, encoded by Adgra3, is an orphan adhesion G-protein coupled receptor (aGPCR) implicated in modulating Wnt signaling and planar polarity. Here we establish both physiological and pathological roles for Gpr125. We show that mice lacking Gpr125 or its signaling domains display an ocular phenotype with many hallmarks of human dry eye syndrome. These include squinting, abnormal lacrimation, mucus accumulation, swollen eyelids and inflammatory infiltration of lacrimal and meibomian glands. Utilizing a Gpr125-β-gal reporter and scRNAseq, we identify Gpr125 expression in a discrete population of cells located at the tips of migrating embryonic lacrimal ducts. By lineage tracing we show these cells function as progenitors of the adult lacrimal myoepithelium. Beyond defining an essential role for Gpr125 in tear film and identifying its utility as a marker of lacrimal progenitors, this study implicates Gpr125 in the etiology of blepharitis and dry eye syndrome, and defines novel animal models of these common maladies.

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CLINICAL AND HISTOPATHOLOGICAL FEATURES OF SCOPOLAMINE HYDROBROMIDE INDUCED DRY EYE SYNDROME IN SPRAGUE-DAWLEY RATS

Taiwan Veterinary Journal ◽

10.1142/s1682648520500134 ◽

2021 ◽

pp. 1-8

Author(s):

Sze-Min Chan ◽

Hui-Wen Chang ◽

Pei-Shiue Tsai ◽

Chian-Ren Jeng ◽

Hao Lee ◽

...

Keyword(s):

Dry Eye ◽

Histopathological Examination ◽

Tear Film ◽

Dry Eye Syndrome ◽

Therapeutic Interventions ◽

Sprague Dawley ◽

Corneal Surface ◽

Fluorescein Staining ◽

Scopolamine Hydrobromide ◽

Volume Assessment

Dry eye syndrome (DES), is one of the most common and irritating ocular diseases in humans and animals due to deficits in quantities or/and quality of tear film. In this study, a rat model of experimental DES has been developed using the cholinergic inhibitor, scopolamine hydrobromide (SCOP), at the dose of 25[Formula: see text]mg/rat/day via subcutaneous injection, for a consecutive 21 days without low humidity environment. Clinical ophthalmic evaluations were performed by tear volume assessment using endodontic paper point, slit-lamp biomicroscope, and fluorescein staining at day 0, 7, 14, and 21 post-inductions. The results of ophthalmic examination showed that rats with SCOP treatment reduced about 40% of tear secretion. Half of the SCOP-treated rats exhibited diffuse corneal fluorescein staining involving 80% of the corneal surface, minimal keratoconjunctivitis, roughened corneal surface and thin corneal epithelium under histopathological examination. About 30% of the rats showed variable infiltration of lymphocytes in between the tubular acinar glands. This animal model with significant reduction of tear production and diffuse corneal fluorescein staining in rats could be used for the preclinical assessment of therapeutic interventions.

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Dry eye syndrome in patients with gout

POINT OF VIEW EAST – WEST ◽

10.25276/2410-1257-2021-4-6-11 ◽

2021 ◽

pp. 6-11

Author(s):

K.N. Odinaeva ◽

◽

N.S. Al Khateeb ◽

M.A. Frolov ◽

◽

...

Keyword(s):

Uric Acid ◽

Correlation Coefficient ◽

Dry Eye ◽

Strong Correlation ◽

Strong Dependence ◽

Tear Film ◽

Dry Eye Syndrome ◽

Film Rupture ◽

High Tendency ◽

Tear Production

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.

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