scholarly journals TLR4-Dependent DUOX2 Activation Triggered Oxidative Stress and Promoted HMGB1 Release in Dry Eye

2022 ◽  
Vol 8 ◽  
Author(s):  
Bowen Wang ◽  
Hao Zeng ◽  
Xin Zuo ◽  
Xue Yang ◽  
Xiaoran Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Dry Eye ◽  
Ocular Surface ◽  
Cell Counting ◽  
Corneal Epithelial Cell ◽  
Rna Seq ◽  
Corneal Epithelial ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Dry eye disease (DED) is one of the most common ocular surface diseases worldwide. DED has been characterized by excessive accumulation of reactive oxygen species (ROS), following significant corneal epithelial cell death and ocular surface inflammation. However, the key regulatory factor remains unclear. In this study, we tended to explore whether DUOX2 contributed to DED development and the underlying mechanism. Human corneal epithelial (HCE) cells were treated with hyperosmolarity, C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Expression of mRNA was investigated by RNA sequencing (RNA-seq) and quantitative real-time PCR (qPCR). Protein changes and distribution of DUOX2, high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and 4-hydroxynonenal (4-HNE) were evaluated by western blot assays and immunofluorescence. Cell death was assessed by Cell Counting Kit-8 (CCK8), lactate dehydrogenase (LDH) release, and propidium iodide (PI) staining. Cellular ROS levels and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. RNA-seq and western blot assay indicated a significant increase of DUOX2 dependent of TLR4 activation in DED both in vitro and in vivo. Immunofluorescence revealed significant translocation of HMGB1 within corneal epithelial cells under hyperosmolar stress. Interestingly, after ablated DUOX2 expression by siRNA, we found a remarkable decrease of ROS level and recovered MMP in HCE cells. Moreover, knockdown of DUOX2 greatly inhibited HMGB1 release, protected cell viability and abolished inflammatory activation. Taken together, our data here suggest that upregulation of DUOX2 plays a crucial role in ROS production, thereafter, induce HMGB1 release and cell death, which triggers ocular surface inflammation in DED.

scholarly journals One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease

2017 ◽  
Vol 27 (6) ◽  
pp. 678-685 ◽  
Author(s):  
Christophe Baudouin ◽  
Maite Sainz de la Maza ◽  
Mourad Amrane ◽  
Jean-Sébastien Garrigue ◽  
Dahlia Ismail ◽  
...  
Keyword(s):  
Dry Eye ◽  
Cyclosporine A ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Efficacy And Safety ◽  
Open Label ◽  
Once Daily ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Purpose The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE). Methods In this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups). Results A total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (≥2 CFS points, ≥30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA. Conclusions In this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.

Evaluation of Ocular Surface Inflammation in the Presence of Dry Eye and Allergic Conjunctival Disease

2005 ◽  
Vol 3 ◽  
pp. S116 ◽  
Author(s):  
Michael E. Stern ◽  
Karyn F. Siemasko ◽  
Jianping Gao ◽  
Margarita Calonge ◽  
Virginia L. Calder ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

scholarly journals Analysis of Clinical Characteristics of Immune-Related Dry Eye

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hua Wang ◽  
Ping-Bao Wang ◽  
Ting Chen ◽  
Jing Zou ◽  
Ya-Jia Li ◽  
...  
Keyword(s):  
Dry Eye ◽  
Lupus Erythematosus ◽  
Ocular Surface ◽  
Clinical Characteristics ◽  
Nerve Fibers ◽  
Immune System Diseases ◽  
Corneal Nerve ◽  
The Difference ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Aim. To discuss the clinical characteristics of immune-related dry eye. Methods. Simple dry eye (SDE) group: we selected 224 patients of simple dry eye with no systemic lesions. Immune-related dry eye (IRDE) group: we selected 207 patients of dry eye complicated with immune system diseases, including 70 cases of Sjögren’s syndrome (SS), 72 cases of systemic lupus erythematosus (SLE), and 65 cases of rheumatoid arthritis (RA). The classification of all patients was performed. The difference between the two groups was compared, including age, gender, ocular surface fluorescein staining and inflammatory reaction, tear breakup time (TBUT), Shirmer I test, confocal microscopy scan, and dry eye grading. Results. Compared with the SDE group, the patients of IRDE group were younger (P<0.05). The female patients were significantly more than the male ones (P<0.05). Corneal staining counts and ocular surface inflammation were significantly increased (P<0.05). TBUT and Shirmer I test shortened significantly (P<0.05). Corneal nerve fibers were less, and the number of local lymphocyte was significant increased. The number of dry eye patients in the moderate or above IRDE group was significantly increased (P<0.05). Conclusions. The dry eye symptom and sign and ocular surface inflammation of IRDE were significantly more severe than those of the SDE.

Corneal autophagy and ocular surface inflammation: A new perspective in dry eye

2019 ◽  
Vol 184 ◽  
pp. 126-134 ◽  
Author(s):  
Shisi Ma ◽  
Zhen Yu ◽  
Songfu Feng ◽  
Huijie Chen ◽  
Haiyan Chen ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
New Perspective ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

The Use of Conjunctival Staining to Measure Ocular Surface Inflammation in Patients With Dry Eye

Cornea ◽  
2019 ◽  
Vol 38 (6) ◽  
pp. 698-705 ◽  
Author(s):  
Soonwon Yang ◽  
Hyun Jung Lee ◽  
Da-Yeong Kim ◽  
Soojung Shin ◽  
Stefano Barabino ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation
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