ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice

Gao, Jianping; Morgan, Grant A.; Tieu, David; Schwalb, Tammy A.; Luo, Jessica Y.; Wheeler, Larry A.; Stern, Michael E.

doi:10.1016/j.exer.2003.10.024

Cited by 99 publications

(63 citation statements)

References 34 publications

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“…Mean age of the CF group was 14.8274.11 years (range 7-23) vs 15.5174.65 years (range [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] in the control group. Only subjects with absolutely normal criteria and not having received any eye drops for at least 3 months were used for normal population analyses.…”

Section: Methodsmentioning

confidence: 99%

“…9 It is known that inflammation plays an essential role in the pathogenesis of dry eye. [9][10][11][12][13][14][15] The human conjunctival epithelium is a nonkeratinized squamous tissue composed of three to five layers that cover 80% of the ocular surface. It has a complex arrangement of microvilli and microplicae and contains goblet cells, Langerhans cells, some lymphocytes, and melanocytes.…”

Section: Introductionmentioning

confidence: 99%

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Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis

Mrugacz

Zak

Bakunowicz-Łazarczyk

et al. 2006

Eye

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Purpose Cystic fibrosis (CF) is an autosomal-recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to investigate the expression of HLA-DR on conjunctival epithelial cells from patients with CF. Materials and methods Twenty-five patients with CF and 25 normal subjects underwent ocular examination. Tear film break-up time (TBUT), Schirmer test, lissamine green staining, and conjunctival impression cytology were carried out. Cells were processed for flow cytometry, by using monoclonal antibodies to HLA-DR. Results The Schirmer test and TBUT scores were significantly lower in CF patients compared with controls. A significant increase of HLA-DR expression on epithelial cells was found in patients with CF compared with normal eyes. The Schirmer and TBUT test were positively correlated with HLA-DR expression for the percentage of cells. Conclusion These results suggest that conjunctival epithelial cells play an important proinflammatory role in ocular changes in CF patients. Our findings confirm the presence of an inflammatory background and the immune nature of this disease. HLA-DR measurement might be a useful method for monitoring of inflammatory processes in the conjunctiva and could be helpful in the use of antiinflammatory drugs in the treatment of ocular findings in CF patients.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis

Mrugacz

Zak

Bakunowicz-Łazarczyk

et al. 2006

Eye

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“…We studied 24 patients with CF (female(F)/ male (M): 13/11) with a mean age of 14.32 6 3.91 years (range [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] presented to the III Department of Pediatric Diseases, Medical University of Bialystok, Poland. Twenty-four normal subjects (F/M: 12/12) with a mean age 13.92 6 3.32 (range 8-21) were also included.…”

Section: Methodsmentioning

confidence: 99%

“…The causes of dry eye are multifactorial and can be related to deficiencies in one of the components of the ocular surface and tear film (5). The involvement of immunological processes in patients with dry eye has been studied in recent years, with participation of intercellular adhesion molecule-1 (ICAM-1) especially (6)(7)(8). ICAM-1 is the member of the immunoglobulin gene family which play a crucial role in communication between lymphocytes and other cells (e.g., epithelial cells) and controlling migration of leukocytes in the inflammatory process (9,10,11).…”

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confidence: 99%

ICAM‐1 expression on conjunctival epithelial cells in patients with cystic fibrosis

Mrugacz

Zak

Bakunowicz-Łazarczyk

et al. 2007

Cytometry Part B Clinical

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Background: Cystic fibrosis is one of the most common lethal genetic conditions. The defect is due to mutations in a gene on chromosome 7, named the cystic fibrosis transmembrane regulator (CFTR), which functions as a chloride channel in epithelial membranes It is presumed that the disease affects all secretory epithelia including the eye. The objective of this study is to investigate the expression of intercellular adhesion molecule-1 (ICAM-1) by conjunctival epithelial cells of patients with cystic fibrosis and the correlation between of the expression of ICAM-1 and the grade of cystic fibrosis severity.Methods: Impression cytology specimens were collected in 24 patients with cystic fibrosis. Cells were processed for flow cytometry, by using monoclonal antibodies to ICAM-1.Results: A significant increase of ICAM-1 expression on epithelial cells was found in patients with cystic fibrosis when compared with normal eyes. A positive correlation between the ICAM-1 expression and severe clinical status of CF patients was also observed.Conclusions: Our findings suggest that the inflammation appears to have a role in the pathogenesis of the ocular surface changes in patients with cystic fibrosis. ICAM-1 expression on conjunctival epithelial cells may be a marker of the inflammatory status in cystic fibrosis patients. The method described here reveal good repeatability and reliability for the analysis of the inflammatory markers on conjunctival epithelial cells and can be a useful tool in evaluating of the ocular findings and treatment interventions in patients with cystic fibrosis. q 2007 Clinical Cytometry Society

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“…13 Also, the increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells of animal models and patients diagnosed with dry eye was observed. 14 Therefore, we postulated that a small molecule LFA-1/ICAM-1 antagonist could offer a targeted T-cell antagonism with improved patient tolerability for such a chronic ocular disease. Recently, we have described the discovery of a series of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists, 15,16 which were shown to bind the I-domain of the CD11a subunit of LFA-1 and serve as direct competitive antagonists of LFA-1 binding to ICAM-1.…”

mentioning

confidence: 99%

Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye

Zhong

Gadek²,

Bui

et al. 2012

ACS Med. Chem. Lett.

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LFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T-cell regulated immune responses by mediating cell adhesion, leukocyte extravasation, migration, antigen presentation, formation of immunological synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells was observed in animal models and patients diagnosed with dry eye. Therefore, it has been hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective topical treatment for dry eye. In this letter, we describe the discovery of a potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118) and its development as an ophthalmic solution for treating dry eye.

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ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice

Cited by 99 publications

References 34 publications

Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis

Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis

ICAM‐1 expression on conjunctival epithelial cells in patients with cystic fibrosis

Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye

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