Immune response in the conjunctival epithelium of patients with dry eye (original) (raw)
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Cytomorphology of the Bulbar Conjunctival Cells in Patients with Dry Eye
Facta Universitatis, Series: Medicine and Biology, 2017
Dry eye is among the most common pathological conditions in ophthalmology. The aim of our study was to present possibilites of two different cytological methods for examination of cytomorphology of bulbar conjunctival cellsimpression cytology (IC) and combined cytological method for scanning electron microscopy in the diagnosis of dry eye (ICSEM). A hundred and twenty-two patients of both sexes, in different age groups, were analyzed by clinical method (slit lamp, Schirmer I, TBUT, Rose Bengal) and two cytomorphological methods-IC and ICSEM. In patients with dry eye, squamous metaplasia, inflammation and severe loss of adhesiveness of the epithelium were present. ICSEM gives an advantage in early diagnosis of changes, before the lesion of superficial conjunctival epithelium in patients with dry eye. The phenomenon of metaplasia appears in the epithelium of the bulbar conjunctiva in the absence of manifest dry eye and represents the basis for understanding the increased incidence of this syndrome in older patients with dry eye.
Lymphocytes in Dry Eye Disease
Dry Eye Syndrome - Modern Diagnostic Techniques and Advanced Treatments, 2022
The eye is a delicate organ that, along with other tissues such as the testicles and brain, is considered immune-privileged. Immune cells that reside in the eye must create a tolerogenic microenvironment to prevent unwanted aggressive inflammatory reactions that can compromise function. However, the eye is exposed to persistent environmental insult that may overwhelm immune tolerance and result in eye diseases from diverse origins (autoimmune, infectious, and inflammatory). The immune system plays a central role in the different phases of eye diseases, as alterations in immune cells in response to mechanical, chemical, or infectious stimuli initiate and amplify the immune response that lead to ocular tissue damage. Both resident and infiltrating immune cells also actively inhibit the immune response and promote tissue repair. Emerging evidence is leading to a better understanding of how and when lymphocytes, amongst other immune cells, contribute to inflammatory diseases such as dry...
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
Developments in ophthalmology, 2010
The physiologically protective mucosal immune system of the ocular surface consists of lymphocytes, accessory leukocytes and soluble immune modulators. Their involvement has also been observed in inflammatory ocular surface diseases, including dry eye syndrome, and we have attempted here to describe their interaction. Our own results regarding the mucosal immune system of the human ocular surface are discussed together with the available literature on mucosal immunity and inflammatory ocular surface disease. The mucosa of the ocular surface proper (conjunctiva and cornea) is anatomically continuous with its mucosal adnexa (the lacrimal gland and lacrimal drainage system) and contains a mucosal immune system termed 'eye-associated lymphoid tissue' (EALT). This extends from the periacinar lacrimal-gland-associated lymphoid tissue along the excretory ducts into the conjunctiva-associated lymphoid tissue (CALT) and further into the lacrimal drainage-associated lymphoid tissue (L...
The Ocular Surface, 2005
The ocular inflammatory diseases dry eye and allergic conjunctivitis are mediated by CD4+ T cells. Th1 cells secrete interferon (IFN)-γ and are implicated in mediating the disease process in dry eye. Allergic conjunctivitis has been classically defined as a Th2 disease because of the predominance of Th2 cytokines interleukin (IL)-4 and IL-13. A multi-hit antigen challenge mouse model of allergic conjunctivitis provides evidence that IFN-γ, a Th1 cytokine, acts as an endothelium gatekeeper by regulating endothelial expression of vascular adhesion molecule-1 required for inflammatory conjunctival cell infiltration. Current research encourages an in-depth evaluation of the exact role Th1 and Th2 cells play in ocular inflammation.
Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye
Investigative ophthalmology & visual science, 2002
To examine the conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca (SS-KCS) and non-Sjögren's keratoconjunctivitis sicca (NS-KCS) for evidence of immune-based inflammation. Conjunctival biopsy specimens were obtained from 15 patients with SS-KCS and 15 with NS-KCS. Immunohistochemistry was performed on frozen sections to characterize and quantify T-cell subtypes (CD3, CD4, and CD8) and markers of immune activation (major histocompatibility complex [MHC] class II: HLA-DR, HLA-DQ) and inflammation (intercellular adhesion molecule [ICAM]-1). The numbers of cells positive for each marker were counted by two masked observers and averaged. Conjunctival biopsy specimens from patients with SS-KCS or NS-KCS revealed lymphocytic infiltration and increased immunoreactivity for the markers of inflammation and immune activation. The extent of cellular immunoreactivity did not differ significantly between SS-KCS and NS-KCS tissue samples. The authors' findings i...
Further Studies on the Immunopathology of Atopic Keratoconjunctivitis using Flow Cytometry
Experimental Eye Research, 1997
Atopic keratoconjunctivitis (AKC) is an ocular manifestation of systemic hypersensitivity. Although the pathogenesis of AKC is not fully understood, some previous data suggest that a decrease in numbers of suppressor T lymphocyte (Ts) and increase of Th, especially Th2 (the second subgroup of helper T lymphocyte), at the ocular surface may play an important role in the occurrence of the disease. In this study, the percentages of naive-Th (CD4\45RAj) and memory-Th (CD4\29j) cells, and the Th\Ts and memory-Th cells\naive-Th cells ratios were measured in the blood and tear samples of patients with AKC, atopic patients without ocular involvement and normal volunteers, using flow cytometry. Groups were compared using the Mann-Whitney U test. We found that patients with AKC had significantly higher memory-Th cell concentration, and Th\Ts and memory-Th cells\naive-Th cell ratios both in the tear and blood samples compared to normal subjects. While no significant difference existed between the tear samples of the atopic patients without ocular involvement and normal volunteers with respect to the above values, atopic patients had higher percentages of memory-Th cells and higher Th\Ts and memory-Th cells\naive-Th ratios in their blood than normal subjects. The percentages of memory-Th cells, and the Th\Ts and memory-Th cells\naive-Th cell ratios in the tear samples of AKC patients were also found to be higher than that of the atopic patients without ocular involvement, but no significant difference was present between the blood samples of these groups. The percentages of naive-Th cells did not show any significant difference between groups either in tear or blood samples. Since the mean memory-Th cells\naive-Th1 cells ratio in the tear samples of the patients with AKC was higher than in their blood samples, we propose that the localized accumulation of memory-Th2 cells, in addition to the increase of Th\Ts ratios in the external eye may cause AKC in atopic individuals.
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 Role of Conjunctival Epithelial Cells in Chronic Ocular Allergic Disease
Experimental Eye Research, 1998
Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experiments were to compare the expression of HLA-DR, ICAM-I and pro-allergic cytokines in conjunctival epithelial cells in the different chronic ocular allergic disorders with each other and with normal subjects. Conjunctiva from normal patients (n l 10) and patients with vernal keratoconjunctivitis (VKC, n l 10), atopic keratoconjunctivitis (AKC, n l 10) and contact lens-associated giant papillary conjunctivitis (GPC, n l 10) were examined by immunohistochemistry. Epithelial cell staining for surface antigens and cytokines was graded by one masked observer using a four point scale based on the percentage of epithelial cells staining positive. There was no expression of ICAM-1 or HLA-DR in the normal conjunctival epithelial cells, but both antigens were induced on conjunctival epithelial cells in the allergic tissue, and there was greater expression in AKC and VKC compared with GPC. Cytokines IL-6, IL-8, RANTES and TNF-α all localised to normal conjunctival epithelial cells. RANTES was upregulated in all the allergic disorders and IL-8 was upregulated in GPC. IL-3 and GM-CSF were not expressed in normal conjunctival epithelial cells. GM-CSF was expressed in all disorders and there was greater expression in AKC compared with GPC and VKC. IL-3 was expressed only in AKC and VKC epithelial cells. These results suggest that conjunctival epithelial cells play an important pro-inflammatory role in chronic ocular allergic diseases ; ICAM-1 may allow epithelial cells to recruit, retain and locally concentrate leukocytes ; the presence of HLA-DR raises the question of conjunctival epithelial cell antigen presentation. The epithelial cytokines which are upregulated are known to promote eosinophilic inflammation and are typical of allergic inflammation. The differences in cytokine patterns may be exploitable for future therapy.