scholarly journals A Ligation of the Lacrimal Excretory Duct in Mouse Induces Lacrimal Gland Inflammation with Proliferative Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Liu ◽  
Masatoshi Hirayama ◽  
Tetsuya Kawakita ◽  
Kazuo Tsubota
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Tissue Injury ◽  
Dry Eye Disease ◽  
Excretory Duct ◽  
Eye Disease ◽  
Injury Model ◽  
Duct Ligation ◽  
Number Of Patients

The lacrimal gland secretes tear fluids to ocular surface, which plays an indispensable role in maintaining the health of the ocular epithelia and protecting the ocular surface from the external environment. The dysfunction of the lacrimal glands causes dry eye disease due to a reduction in tear volume. The dry eye disease is becoming a popular public disease, for the number of patients is increasing, who have subjective symptom and loss of vision, which affect the quality of life. Inflammatory change in the damaged lacrimal gland has been reported; however, a major challenge is to establish a simple animal model to observe the changes. Here, we demonstrated an injury model by ligating the main excretory duct of the lacrimal gland, which is a simple and stable way to clearly understand the mechanism of lacrimal gland inflammation. We observed the process of injury and proliferation of the lacrimal gland and detected a population of lacrimal gland epithelial cells with proliferation potential which were also nestin-positive cells following duct ligation. This study successfully established an injury model to observe the tissue injury process of the lacrimal gland, and this model will be useful for analysis of the inflammation and proliferation mechanism in the future.

scholarly journals Defining Dry Eye from a Clinical Perspective

2020 ◽  
Vol 21 (23) ◽  
pp. 9271
Author(s):  
Kazuo Tsubota ◽  
Stephen C. Pflugfelder ◽  
Zuguo Liu ◽  
Christophe Baudouin ◽  
Hyo Myung Kim ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Surrogate Endpoint ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Consensus Definition ◽  
Number Of Patients ◽  
Definition Of

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.

scholarly journals MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jana Dietrich ◽  
Lolita Ott ◽  
Mathias Roth ◽  
Joana Witt ◽  
Gerd Geerling ◽  
...  
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Immune Reaction ◽  
Tear Film ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Duct Ligation ◽  
Promising Therapeutic Approach ◽  
High Prevalence ◽  
Surgically Induced

AbstractDry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.

Comparative analysis on the dynamic of lacrimal gland damage and regeneration after Interleukin-1α or duct ligation induced dry eye disease in mice

2018 ◽  
Vol 172 ◽  
pp. 66-77 ◽  
Author(s):  
Jana Dietrich ◽  
Carlo Schlegel ◽  
Mathias Roth ◽  
Joana Witt ◽  
Gerd Geerling ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Duct Ligation ◽  
Interleukin 1Α

scholarly journals Therapeutical approach to dry eye syndrome

2010 ◽  
Vol 63 (11-12) ◽  
pp. 793-800 ◽  
Author(s):  
Gordana Stankovic-Babic ◽  
Gordana Zlatanovic ◽  
Jasmina Djordjevic-Jocic ◽  
Sonja Cekic ◽  
Milena Vujanovic
Keyword(s):  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Cell Damage ◽  
Tear Film ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Inflammatory Disorder ◽  
Therapeutic Modalities ◽  
Third Line

Introduction. Dry eye disease or dysfunctional tear syndrome is among the most frequently established diagnoses in ophthalmology. It can be defined as a disorder of the tear film resulting in changes in the ocular surface. Mechanisms in development of dry eye disease. There are many factors causing dry eye and they can be related to deficiency in any of the components of the tear film. It has been suggested that dry eye is an inflammatory disorder that affects the ocular surface and lacrimal gland. Inflammation is the most important mechanism of corneal and conjunctival cell damage, which is responsible for the symptoms and signs of ocular surface pathology. Hormonal imbalance (particularly androgens), neural dysfunction, increased levels of pro-inflammatory cytokines and loss of immune homeostasis of the lacrimal gland and ocular surface could be possible mechanisms in the pathogenesis of dry eye disease. Discussion. The aim of this paper was to review the advances in the pathogenesis and management of the dry eye disease. The appropriate dry eye treatment presupposes knowledge of all existing pharmacologic and non-pharmacologic therapeutic modalities. The mainstay of therapy is still artificial tears, with anti-inflammatory therapy and punctual occlusion therapy as second and third line therapies.

scholarly journals The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

2021 ◽  
Vol 13 ◽  
pp. 251584142110127
Author(s):  
Preeya K. Gupta ◽  
Nandini Venkateswaran
Keyword(s):  
Drug Delivery ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Short Term ◽  
Short Term Treatment ◽  
Loteprednol Etabonate ◽  
Mucus Barrier

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film’s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.

scholarly journals Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 905
Author(s):  
Sangeeta Kumari ◽  
Madhuri Dandamudi ◽  
Sweta Rani ◽  
Elke Behaeghel ◽  
Gautam Behl ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Pilot Scale ◽  
Dry Eye Disease ◽  
Rapid Screening ◽  
Eye Disease ◽  
Topical Steroids ◽  
Nanostructured Lipid Carrier ◽  
The Impact ◽  
Ophthalmic Formulation

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

scholarly journals Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt as the Representative Eye for the Study?

2021 ◽  
Vol 22 (1) ◽  
pp. 422
Author(s):  
Ming-Tse Kuo ◽  
Po-Chiung Fang ◽  
Shu-Fang Kuo ◽  
Alexander Chen ◽  
Yu-Ting Huang
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Mechanistic Studies ◽  
Clinical Tests ◽  
Tear Proteins ◽  
Proteomic Data ◽  
Surface Performance

Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye’s performance cannot represent that of the other eye or both eyes. Therefore, in studies for elucidating tear film homeostasis of DED, we may lose some important messages hidden in the fellow eye if we collected clinical and proteomic data only from a unilateral eye. For mechanistic studies, it is recommended that researchers collect tear samples from the eye with more severe DED under sensitive criteria for identifying the more severe eye and evaluating the tear biochemical and proteomic markers with binocular concordance drawn in prior binocular studies.

scholarly journals A Survey on How Ocular Surface Demodex Infestation Interactively Associates with Diabetes Mellitus and Dry Eye Disease

2021 ◽  
Author(s):  
Chang Huang ◽  
Shuze Chen ◽  
Sheng Fu ◽  
Yingli Li ◽  
Zhenhao Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dry Eye ◽  
Ocular Surface ◽  
Cross Sectional Study ◽  
General Information ◽  
Potential Interaction ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Cross Sectional ◽  
Demodex Infestation

Abstract Purpose Prevention of ocular surface (OS) Demodex infestation plays an important role in OS hygiene and variety of factors may be associated with it, in which diabetes mellitus (DM) or dry eye disease (DED) has caught the attention of most scholars. However, there has been no research on whether there was a potential interaction between DM and DED in the process of OS Demodex infestation. This cross-sectional study was implemented in Zhujiang Hospital of Southern Medical University. Methods Ophthalmologic interviews, questionnaires, and examinations were conducted. Factors including general information, DM status, dry eye condition, etc. were collected to study the correlation of DM and DED on OS Demodex infestation. Results After statistical analysis, we found that both DM (P < 0.001) and DED (P = 0.013 < 0.05) are closely associated with OS Demodex infestation. Compared with DED, DM has higher priority association with OS Demodex infestation, and patients with both diseases have a significant higher risk of OS Demodex infestation (R = 0.197, P < 0.001). Meanwhile, age (R = 0.299, P < 0.001) and hypertension (P < 0.05) were also correlated with OS Demodex infestation. Conclusion This study provides a new evidence-based basis for clinical prevention and management of OS Demodex infestation.

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