Interleukin-8 Concentrations in Conjunctival Epithelium Brush Cytology Samples Correlate With Neutrophil, Eosinophil Infiltration, and Corneal Damage

Miyoshi, Takahiro; Fukagawa, Kazumi; Shimmura, Shigeto; Fujishima, Hiroshi; Takano, Yasushi; Takamura, Etsuko; Tsubota, Kazuo; Saito, Hirohisa; Oguchi, Yoshihisa

doi:10.1097/00003226-200110000-00014

Cited by 47 publications

(21 citation statements)

References 12 publications

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“…Moreover, the impression cytology and brush cytology samples can also be used to perform immunohistochemical staining, enzyme-linked immunosorbent assay, flow cytometry, and mRNA expression analysis. 9,10,29,30 Therefore, they are also useful to monitor the pathologic progress in cGVHD-related dry eye disease and helpful for investigating the etiology of cGVHD-related dry eye disease.…”

Section: Discussionmentioning

confidence: 99%

“…7 They are noninvasive, repeatable, and useful in following the changes in the ocular surface. 8,9 However, there are few reports on impression cytology changes and brush cytology characteristics in patients with cGVHD-related dry eye. 10 On the other hand, the conditioning regimen including total body irradiation and high incidence of meibomian gland dysfunction (MGD) in post-GVHD patients contributes to the ocular surface and tear function changes.…”

Section: Introductionmentioning

confidence: 99%

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Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Wang

Ogawa

Doğru

et al. 2009

Bone Marrow Transplant

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We evaluated ocular surface alterations in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with or without chronic GVHD-related dry eye in a prospective study. Fifty eyes of 25 post-HSCT patients and 28 eyes of 14 age-matched healthy controls were included. Meibomian gland (MG) obstruction, tear evaporation rate, corneal sensitivity (CS), Schirmer test-I, tear break-up time (BUT) and ocular surface vital staining were examined. Conjunctival impression and brush cytology specimens were collected to evaluate the goblet cell density (GCD) and the inflammatory cell numbers. Obvious MG obstruction, decreased CS and enhanced tear evaporation rate were found in post-HSCT patients compared with normal controls. In addition, decreased conjunctival GCD, increased conjunctival squamous metaplasia and inflammatory cells were noted in cGVHD-related dry eyes compared with normal controls and post-HSCT without dry eye subjects. Furthermore, the conjunctival inflammatory cells were significantly higher in severe dry eyes compared with mild dry eyes (P ¼ 0.03). We found comprehensive ocular surface alteration in post-HSCT patients, regardless of whether they had cGVHD-related dry eye or not. The results suggest that the extent of inflammatory process seems to have a pivotal role in the outcome of the cGVHD-related dry eye.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Wang

Ogawa

Doğru

et al. 2009

Bone Marrow Transplant

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“…The inflammation was reported as the percentage of inflammatory cells present in the 500 cells counted. 22,24 Quantitative real-time RT-PCR for MUC5AC Quantitative real-time RT-PCR was performed as described previously. 23 Briefly, RNA was extracted from Topical cyclosporine in dry eye in patients with cGVHD Y Wang et al Isogen samples and quantitative real-time PCR was performed according to the manufacturer's instructions (Applied Biosystems, Weiterstadt, Germany).…”

Section: Impression Cytology Parametersmentioning

confidence: 99%

Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease

Wang

Ogawa

Doğru

et al. 2007

Bone Marrow Transplant

108

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We investigated the effect of 0.05% topical cyclosporine (Cys) on the ocular surface and tear functions in dry eye patients with chronic GVHD (cGVHD) in a prospective comparative study. Thirty eyes of 15 patients refractory to baseline treatment were recruited and the patients assigned for topical Cys treatment group (14 eyes of 7 patients) and control group (12 eyes of 6 patients) respectively. Two patients dropped out because of intolerable irritation while using topical Cys eye drops. Visual analog scale symptom scores, corneal sensitivity, Schirmer I test value, tear film break-up time (TBUT), tear evaporation rate and ocular surface vital staining scores were recorded at baseline and at the end of the following one month. Conjunctival impression and brush cytology were performed before and after the treatment. After topical Cys treatment, significant improvements were found in symptom scores, corneal sensitivity, tear evaporation rate, TBUT, vital staining scores, goblet cells density, conjunctival squamous metaplasia grade, inflammatory cell numbers and the MUC5AC expression. Our study suggests that 0.05% topical Cys may be an effective treatment for dry eye patients with cGVHD. The improvements in the ocular surface and tear functions resulted presumably from the decreased inflammation, increased goblet cell density and MUC5AC mRNA expression.

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“…It has been reported that the infiltration of inflammatory cells such as mast cells, eosinophils, neutrophils, and T cells were detected in the papillae of VKC patients. [4][5][6][7][8] Therefore, in addition to immunoglobulin E (IgE)-mediated allergy induced by mast cells, a late phase reaction mediated by eosinophils and delayed-type allergy induced by T cells are thought to be involved in VKC induction.Fukushima et al reported the inhibitory effect of CyA eye drops on eosinophil infiltration in a mouse allergic conjunctivitis model. 9) We have also reported that the instillation of CyA inhibited neutrophil infiltration into the conjunctiva in a delayed-type allergic conjunctivitis model in guinea pigs.…”

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confidence: 99%

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

Shii

Nakagawa

Yoshimi

et al. 2010

Biological & Pharmaceutical Bulletin

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Cyclosporine A (CyA) is a cyclic polypeptide calcineurin inhibitor that was first purified in the 1970s by Novartis Pharma (formerly Sandoz Pharma, Switzerland) from cultures of the fungus Tolypocladium inflatum. It has long been a trusted agent for suppressing not only graft rejection after transplantation, but also immune reaction disorders often observed in autoimmune diseases. The therapeutic effects of CyA eye drops in the treatment of vernal keratoconjunctivitis (VKC), one of the most severe refractory allergic conjunctival diseases, have been described in several studies. [1][2][3] VKC involves severe allergic inflammation sufficient to cause the formation of proliferative conjunctival giant papillae, hyperemia, edema, swelling, mucous discharge and corneal damage. It has been reported that the infiltration of inflammatory cells such as mast cells, eosinophils, neutrophils, and T cells were detected in the papillae of VKC patients. [4][5][6][7][8] Therefore, in addition to immunoglobulin E (IgE)-mediated allergy induced by mast cells, a late phase reaction mediated by eosinophils and delayed-type allergy induced by T cells are thought to be involved in VKC induction.Fukushima et al. reported the inhibitory effect of CyA eye drops on eosinophil infiltration in a mouse allergic conjunctivitis model. 9) We have also reported that the instillation of CyA inhibited neutrophil infiltration into the conjunctiva in a delayed-type allergic conjunctivitis model in guinea pigs. 10)However, the efficacy of CyA eye drops in treating the symptoms in these allergic conjunctivitis models has not been previously reported. Therefore, to understand how CyA works in VKC therapy, we investigated the effects of CyA eye drops on ocular symptoms in late phase and delayed-type allergic conjunctivitis models in guinea pigs. Animals Five-week-old male guinea pigs (Hartley, Nippon SLC, Shizuoka, Japan) were housed under a 12-h light-12-h dark cycle (07:00-19:00 h), with room temperature maintained at 23Ϯ3°C and humidity at 50Ϯ20%. Food and water were given ad libitum. All experiments were performed in accordance with the Association for Research in Vision and Ophthalmology statement for the Use of Animals in Ophthalmic and Vision Research and approved by the Santen Institutional Animal Care and Use Committee. MATERIALS AND METHODS ReagentsInduction of Late Phase Reaction in the Allergic Conjunctivitis Model Allergic conjunctivitis was induced using the method of Sengoku et al.,11) with some modification. OVA solution (40 mg/ml dissolved in saline) was emulsified with an equal volume of FCA. Then, 1 ml of the mixture was intraperitoneally injected into guinea pigs on days 0 and 7. Twenty-four days after the first immunization, 10 ml of 15% OVA solution was applied topically to the right eye to elicit an allergic reaction. Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis ModelsDaisuke SHII,* Shizu NAKAGAWA, Miwa YOSHIMI, Osamu KATSUTA, Tomoko ODA, and Masat...

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Interleukin-8 Concentrations in Conjunctival Epithelium Brush Cytology Samples Correlate With Neutrophil, Eosinophil Infiltration, and Corneal Damage

Abstract: IL-8 in the extracellular space of the conjunctival epithelium may play a role in the recruitment of neutrophils and possibly eosinophils and in the pathogenesis of corneal damage in severe allergic diseases.

Cited by 47 publications

References 12 publications

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

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