Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye

2013 ◽  
Vol 54 (12) ◽  
pp. 7557 ◽  
Author(s):  
Yong Woo Ji ◽  
Yu Jeong Byun ◽  
Wungrak Choi ◽  
Eunae Jeong ◽  
Jin Sun Kim ◽  
...  
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Tnf Α

scholarly journals In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3245
Author(s):  
Sung-Chul Hong ◽  
Jung-Heun Ha ◽  
Jennifer K. Lee ◽  
Sang Hoon Jung ◽  
Jin-Chul Kim
Keyword(s):  
Animal Model ◽  
Er Stress ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Inflammatory Responses ◽  
Dry Eye Syndrome ◽  
Inhibitory Effects ◽  
Food Material

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.

scholarly journals The Protective Effect of Polygonum cuspidatum (PCE) Aqueous Extract in a Dry Eye Model

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1550 ◽  
Author(s):  
Bongkyun Park ◽  
Ik Lee ◽  
Soo-Wang Hyun ◽  
Kyuhyung Jo ◽  
Tae Lee ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Aqueous Extract ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Corneal Epithelial Cell ◽  
Heme Oxygenase 1 ◽  
Polygonum Cuspidatum

Dry eyes are caused by highly increased osmolarity of tear film, inflammation, and apoptosis of the ocular surface. In this study, we investigated the effect of Polygonum cuspidatum (PCE) aqueous extract in in vivo and in vitro dry eye models. Dry eye was induced by excision of the lacrimal gland and hyperosmotic media. In vivo, oral administration of PCE in exorbital lacrimal gland-excised rats recovered tear volume and Mucin4 (MUC4) expression by inhibiting corneal irregularity and expression of inflammatory cytokines. In vitro, hyperosmotic media induced human corneal epithelial cell (HCEC) cytotoxicity though increased inflammation, apoptosis, and oxidative stress. PCE treatment significantly inhibited expression of cyclooxygenase-2 and inflammatory cytokines (interleukin-6 and tumor necrosis factor-α), and activation of NF-κB p65 in hyperosmolar stress-induced HCECs. Hyperosmolarity-induced increase in Bcl-2-associated X protein (BAX) expression and activation of cleaved poly (ADP-ribose) polymerase and caspase 3 were attenuated in a concentration-dependent manner by PCE. PCE treatment restored anti-oxidative proteins such as heme oxygenase-1 (HO-1), superoxide dismutase-1 (SOD-1), and glutathione peroxidase (GPx) in hyperosmolar stress-induced HCECs. These data demonstrate that PCE prevents adverse changes in the ocular surface and tear fluid through inhibition of hyperosmolar stress-induced inflammation, apoptosis, and oxidation, suggesting that PCE may have the potential to preserve eye health.

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye

2018 ◽  
Vol 28 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Elisa I. Postorino ◽  
Laura Rania ◽  
Emanuela Aragona ◽  
Carmen Mannucci ◽  
Angela Alibrandi ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Hyaluronic Acid ◽  
Dry Eye ◽  
Coenzyme Q10 ◽  
Ocular Surface ◽  
Fundus Examination ◽  
Ocular Surface Disease Index ◽  
Corneal Confocal Microscopy ◽  
Group A

Purpose: Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). Methods: Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. Results: At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. Conclusions: The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

scholarly journals Role of ion channels in the functional response of conjunctival goblet cells to dry eye

2018 ◽  
Vol 315 (2) ◽  
pp. C236-C246 ◽  
Author(s):  
Donald G. Puro
Keyword(s):  
Ion Channels ◽  
Dry Eye ◽  
Ocular Surface ◽  
Adaptive Response ◽  
Tear Film ◽  
Goblet Cells ◽  
Cation Conductance ◽  
Conjunctival Goblet Cells

Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing >70% of the eye’s refractive power. However, for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye. In freshly excised rat conjunctiva, perforated-patch recordings demonstrated that a ≥10% rise in osmolarity triggers goblet cells to rapidly generate a ~15-mV hyperpolarization due to the oxidant-dependent activation of ATP-sensitive K+ (KATP) channels. High-resolution membrane capacitance measurements used to monitor exocytosis revealed that this hyperpolarization results in an approximately fourfold boost in exocytotic activity evoked by cholinergic input, which in vivo occurs via a neural reflex and depends chiefly on calcium influxing down its electro-gradient. We discovered that this adaptive response is transient. During 30–80 min of hyperosmolarity, development of a depolarizing nonspecific cation conductance fully counterbalances the KATP-driven hyperpolarization and thereby eliminates the exocytotic boost. We conclude that hyperosmotic-induced hyperpolarization is a previously unappreciated mechanism by which goblet cells respond to transient ocular dryness. Loss of this voltage increase during long-term dryness/hyperosmolarity may account for the clinical conundrum that goblet cells in chronically dry eyes can remain filled with mucin even though the tear film is hyperosmotic and mucin-deficient.

scholarly journals Review: The Lacrimal Gland and Its Role in Dry Eye

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Christopher D. Conrady ◽  
Zachary P. Joos ◽  
Bhupendra C. K. Patel
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Tear Film ◽  
Burning Pain ◽  
Layered Coating ◽  
Accessory Glands ◽  
Multiple Components ◽  
Blurry Vision

The human tear film is a 3-layered coating of the surface of the eye and a loss, or reduction, in any layer of this film may result in a syndrome of blurry vision and burning pain of the eyes known as dry eye. The lacrimal gland and accessory glands provide multiple components to the tear film, most notably the aqueous. Dysfunction of these glands results in the loss of aqueous and other products required in ocular surface maintenance and health resulting in dry eye and the potential for significant surface pathology. In this paper, we have reviewed products of the lacrimal gland, diseases known to affect the gland, and historical and emerging dry eye therapies targeting lacrimal gland dysfunction.

scholarly journals Effect of Autologous Serum Eye Drops in Patients with Sjögren Syndrome-related Dry Eye: Clinical and In Vivo Confocal Microscopy Evaluation of the Ocular Surface

In Vivo ◽  
2016 ◽  
Vol 30 (6) ◽  
pp. 931-938 ◽  
Author(s):  
FRANCESCO SEMERARO ◽  
ELIANA FORBICE ◽  
GIUSEPPE NASCIMBENI ◽  
MARCO TAGLIETTI ◽  
VITO ROMANO ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Dry Eye ◽  
Ocular Surface ◽  
Sjögren Syndrome ◽  
Autologous Serum ◽  
Sjogren Syndrome ◽  
Eye Drops ◽  
In Vivo Confocal Microscopy ◽  
Serum Eye Drops

scholarly journals Changes of Dry Eye Related Markers and Tear Inflammatory Cytokines After Upper Blepharoplasty

2021 ◽  
Vol 8 ◽  
Author(s):  
Songjiao Zhao ◽  
Nan Song ◽  
Lan Gong
Keyword(s):  
Inflammatory Cytokines ◽  
Dry Eye ◽  
Ocular Surface ◽  
Clinical Manifestations ◽  
Tear Film ◽  
Ocular Surface Disease Index ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Break Up ◽  
Upper Blepharoplasty

Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty.Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined.Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p &lt;0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively).Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.

scholarly journals Analysis of tear inflammatory molecules and clinical correlations in evaporative dry eye disease caused by meibomian gland dysfunction

2020 ◽  
Vol 40 (11) ◽  
pp. 3049-3058
Author(s):  
Xingdi Wu ◽  
Xiang Chen ◽  
Yajuan Ma ◽  
Xueqi Lin ◽  
Xuewen Yu ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Healthy Subjects ◽  
Meibomian Gland ◽  
Meibomian Gland Dysfunction ◽  
Surface Parameters ◽  
Tnf Α ◽  
Evaporative Dry Eye ◽  
Ifn Γ ◽  
Inflammatory Molecules

Abstract Purpose To compare the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction (MGD)-related evaporative dry eye (EDE) and healthy subjects and to analyze the correlations between the levels of tear inflammatory molecules and ocular surface parameters. Methods A total of 30 MGD-related EDE patients (48 eyes) and ten healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. Results Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100% of the patients, while IL-1α, IL-1β and IL-10 were detected in 56.25%, 13.60% and 45.83% of the patients, respectively. Moreover, ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67–100% of the healthy subjects, and the detection rates of IL-10, IL-1α and IL-1β were below 50%. The levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group. In addition, IL-8 and IL-6 were negatively correlated with Schirmer I test. Besides, IFN-γ was negatively correlated with tear film breakup time. Furthermore, ICAM-1 and IL-6 were positively correlated with meibography score. Conclusions Collectively, patients with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. These findings suggested that inflammation played an important role in MGD-related EDE, and several inflammatory molecules could be used in the diagnosis and the treatment of MGD-related EDE.

scholarly journals The Effect of the Aqueous Extract of Bidens Pilosa L. on Androgen Deficiency Dry Eye in Rats

2016 ◽  
Vol 39 (1) ◽  
pp. 266-277 ◽  
Author(s):  
Chuanwei Zhang ◽  
Kai Li ◽  
Zichao Yang ◽  
Yuliang Wang ◽  
Haipeng Si
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Tear Film ◽  
Phenol Red ◽  
Androgen Deficiency ◽  
Bidens Pilosa ◽  
Fluorescein Staining ◽  
Tnf Α

Background/Aims: Bidens pilosa L. (Bp) is widely distributed in China and has been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of the extract of Bp on androgen deficiency dry eye and determine its possible mechanisms. Methods: Twenty-four rats were randomly divided into four groups: Group Con (control), Group Sal (physiological saline), Group Fin (oral finasteride), and Group Bp (oral finasteride and Bp). The dry eye model was established in group Fin and group Bp. Aqueous tear quantity was measured with phenol red-impregnated cotton threads with anesthesia. Tear film breakup time (BUT) and corneal epithelial damage were evaluated by fluorescein staining. Animals were sacrificed at 28 days, and ocular tissues (lacrimal gland and cornea) were evaluated with light microscopy; gene microarray analysis for inflammatory cytokines and Western blot were also performed. Results: Finasteride administration effectively induced dry eye in rats by 14 days after administration. Group Fin rats had significantly higher fluorescein staining scores and lower aqueous tear quantity and BUT than the group Con rats, and notable inflammatory cell infiltrates were observed in the lacrimal gland of group Fin rats. The fluorescein staining score, aqueous tear quantity and BUT significantly improved with Bp treatment in the group Bp rats, and the structures of the lacrimal gland were well maintained without significant lymphocyte infiltration. Cytokine antibody array data identified the cytokines B7-2/Cd86, IL-1β, IL-4, IL-6, IL-10, MMP-8, FasL, TNF-α and TIMP-1 as candidates for validation by Western blot. Expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in group Fin were upregulated compared with group Con. Levels of anti-inflammatory cytokines, such as IL-4 and IL-10, in group Fin were also upregulated compared with those in group Con. Compared with group Fin, IL-1β, FasL, and TNF-α were significantly decreased in group Bp. Conclusion: The extract of Bp appears to be effective for the treatment of androgen deficiency dry eye in rats by improving aqueous tear quantity, maintaining tear film stability, and inhibiting the inflammation of the lacrimal gland.

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