Pigment Epithelium–Derived Factor Enhances the Suppressive Phenotype of Regulatory T Cells in a Murine Model of Dry Eye Disease (original) (raw)
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Molecular evidence for the role of inflammation in dry eye disease
Clinical and Experimental Optometry, 2019
Ocular surface inflammation is propagated by a complex series of molecular processes and has been implicated in the pathogenesis of dry eye disease (DED), either as a causal or a downstream effect of ocular surface disease. A state of hyperosmolarity elicits an acute immune response in DED, leading to subsequent activation of the adaptive immune response. This cascade incites dysregulation of the immune system, triggering a vicious cycle of events that causes damage to the ocular surface. Symptoms associated with these events include burning, irritation, redness, photophobia and blurred vision. The chronic nature of the disease process can cause permanent alterations to the ocular surface and adnexa. An increasing investment in treatment options, and positive outcomes with novel therapies that have received subsequent regulatory approval, lends further support to the role of inflammation in DED. This review highlights the nature and function of a range of fundamental inflammatory molecules in DED to provide the clinician with an appreciation for the ways in which these factors might be manipulated in DED management.
Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting
Acta ophthalmologica, 2017
Dry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED-related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase-9, human leucocyte antigen-DR or intercellular adhesion molecule-1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on ...
The Ocular Surface, 2020
Purpose-In this study, we quantify Pigment Epithelium-derived Factor (PEDF) secreted by corneal epithelial cells and its immunomodulatory functions in a murine model of dry eye disease (DED). Methods-We induced DED in female C57BL/6 mice using controlled environment chamber for 14 days. We quantified mRNA expression of Serpinf1 gene and PEDF protein expression by corneal epithelial cells (CEpCs) using RT-PCR and ELISA. CEpCs from normal or DED mice were cultured with IFNγ-stimulated-dendritic cells (DCs) for 24 hours, and expression of MHC-II and CD86 by DCs was determined using flow cytometry. Next, we either added recombinant PEDF (rPEDF) or anti-PEDF antibody to co-culture, and DC expression of the above maturation markers was quantified. Lastly, we treated DED mice with either topical rPEDF, anti-PEDF Ab or murine serum albumin (MSA), and DC maturation, expression of pro-inflammatory cytokines, and DED severity were investigated. Results-Serpinf1 mRNA and PEDF protein expression levels by CEpCs were upregulated in DED. CEpCs from DED mice exhibited an enhanced suppressive effect on the expression of MHC-II and CD86 by DCs, compared to normal mice. This effect was abolished by blocking endogenous PEDF with anti-PEDF Ab or enhanced by supplementing with rPEDF. Treatment with anti-PEDF antibody blocked the effect of endogenous-PEDF and increased DC maturation, expression of pro-inflammatory cytokines in conjunctivae, and exacerbated disease severity. Conversely, topical rPEDF enhanced the suppressive effect of endogenous PEDF on DC
Report of the TFOS/ARVO Symposium on Global Treatments for Dry Eye Disease: An Unmet Need
The Ocular Surface, 2012
In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by the Association for Research in Vision & Ophthalmology (www.arvo.org). The Symposium objectives were two-fold: first, to discuss accepted and emerging clinical endpoints of DED with regulatory experts from around the world; and second, to consider how to improve clinical trials of treatments for DED. The Symposium focused on the personal and collective burden of DED, as well as the developmental and regulatory challenges associated with generating new DED therapeutics. This article provides a synopsis of many of the presentations, discussions and recommendations of this Symposium.
Investigative Ophthalmology & Visual Science, 2011
PURPOSE. To assess cell viability and cell cycle kinetics of the conjunctival epithelium and to identify intraepithelial lymphocyte (IEL) subsets in patients with evaporative-type dry eye disease (ev-DED) caused by meibomian gland dysfunction and in healthy subjects. The effect of topical treatment and correlations between clinical symptoms and signs and epithelial and immune variables were also determined. METHODS. Inferior fornix and tarsal conjunctival cells were collected by brush cytology (BC) from patients with mild to moderate ev-DED (n ϭ 23) before and after 2 months of treatment that included lid hygiene, artificial tears, and a 3-week course of topical unpreserved steroids. Healthy subjects (n ϭ 17) served as controls. Two symptom questionnaires were self-answered, and multiple DED-related clinical tests were performed. Epithelial or immune lineage, IEL subtypes, cell viability, apoptosis, and cell cycle stage of the BC-recovered cells were determined by flow cytometry. RESULTS. Conjunctival cell viability was dramatically decreased in ev-DED patients compared with controls. For both groups, two different cell populations, differentiated by cell size and complexity, were present in the apoptosis assay. After 2 months of treatment, 87% of subjects subjectively improved, CD8 cells increased, and CD4 cells and the CD4/CD8 ratio significantly decreased. The pretreatment and posttreatment proliferative capacity of the conjunctival epithelium was significantly lower in ev-DED patients than in healthy controls. CONCLUSIONS. The viability and proliferative capacity of ev-DED patient conjunctival cells were reduced, suggesting a potential role for these parameters as disease biomarkers. (Invest Ophthal
British Journal of Ophthalmology
Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient’s clinical prese...