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Koh-Hei Sonoda

Publications and source records attributed to Koh-Hei Sonoda.

At least 19 recordsLinked to original sources
PubMed2006

WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis.

WSX-1 is a subunit of the IL-27R, which plays a critical role in the initiation of T(h)1 responses. Murine experimental autoimmune uveitis (EAU) is a model of human autoimmune uveitis, in which a T(h)1 response predominates in the pathogenetic process. To explore the role of WSX-1 in this model, WSX-1(-/-) mice were immunized with interphotoreceptor retinoid-binding protein peptide 1-20 to induce EAU. We found that the EAU clinical and histological scores were lower in the WSX-1(-/-) mice up to day 21, whereas after day 21, the EAU scores were the same between the wild-type (WT) and WSX-1(-/-) mice with both declining at the same rate. In contrast to T lymphocytes from WT mice, WSX-1(-/-) T lymphocytes on day 9 after immunization failed to produce IFN-gamma. Similarly, expression of T(h)1-related chemokines, such as regulated on activation, normal T cell expressed and secreted and IP-10, in the eye was reduced in WSX-1(-/-) mice compared with WT mice on day 13 after immunization. In addition, sub-retinal transfer of lymphocytes from WSX-1(-/-) mice on day 9 after immunization did not induce EAU in the recipient mice. Importantly, IFN-gamma production, chemokine expression and the transferability of disease by lymphocytes became comparable for WSX-1(-/-) and WT mice at later stages. Thus, IL-27/WSX-1 affects the early development of EAU, and might be a target for therapy during the onset of autoimmune uveitis in humans.

Animals↗
PubMed2006

Granulocytapheresis in patients with refractory ocular Behcet's disease.

Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD) and responds poorly to drug therapy. This open prospective study was to assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients aged 20-56 years were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carries or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The total numbers of ocular attacks (OA) were monitored for 6 months before and after 5 Adacolumn sessions. The number of OA (mean +/- SD) per patient for the 6 months before Adacolumn was 4.21 +/- 1.6 and for the 6 months post Adacolumn was 2.93 +/- 1.39 ( P = 0.0275). Nine patients (64%) improved and 5 did not change or worsened. Further, for a sub-group (n = 7) with duration of BD > or =5 years, the number of OA were 4.71 +/- 1.89 for the first 6 months and 2.29 +/- 1.38 for the second 6 months ( P = 0.0054). The corresponding values for a sub-group (n = 7) with duration of BD<5 years were 3.71 +/- 1.25 and 3.57 +/- 1.13, indicating that patients with long duration of BD are better responders. We conclude that granulocytapheresis might be effective and safe for patients with refractory ocular BD. Further studies are necessary to fully evaluate the clinical efficacy of granulocytapheresis for BD.

Adult↗
PubMed2006

Gene transfer to corneal epithelium and keratocytes mediated by ultrasound with microbubbles.

PURPOSE: The cornea is an ideal organ for evaluating gene transfer because it can be treated noninvasively and monitored easily. The present study was performed to investigate the practical efficacy and safety of ultrasound (US) plus microbubble (MB)-mediated gene transfer to cornea. METHODS: Cultured rabbit corneal epithelial (RC-1) cells were incubated in 24-well dishes with plasmid DNA having a green fluorescent protein (GFP) gene under a cytomegalovirus promoter. The cells were exposed to US under different intensities (1 MHz; power, 0.5 approximately 2 W/cm2; duration, 15-120 seconds; duty cycle, 20%-100%). The effect of simultaneous stimulation with MBs was also examined. Gene transfer was quantified by counting the number of GFP-positive cells under microscopy. Furthermore, in vivo gene transfer was examined by GFP plasmid injection into rabbit cornea and US exposure with MBs. RESULTS: In the in vitro study, DNA exposure alone could not transfer gene into cultured RC-1 cells; US enhanced gene transfer slightly. Coexposure with MBs significantly increased gene transfer efficiency. In the in vivo study, DNA injection alone could transfer the gene to a limited degree, but plasmid injection plus US with MBs strongly increased gene transfer efficiency without apparent tissue damage, and gene transfer was achieved two dimensionally. CONCLUSIONS: US with MBs greatly increases gene transfer to in vivo and in vitro corneal cells. This noninvasive gene transfer method may be a useful tool for clinical gene therapy.

Animals↗
PubMed2005

CXCR2 Expression on neutrophils is upregulated during the relapsing phase of ocular Behcet disease.

PURPOSE: To search for markers of Behcet disease (BD) activity,we measured CXCR1 and CXCR2 levels on the circulating leukocytes of patients suffering from ocular BD. METHODS: Peripheral blood leukocytes were harvested from healthy volunteers (n = 16) and ocular BD patients (n = 35). The patients consisted of 15 individuals in relapsing phase (6 with prednisolone treatment) and 20 individuals in remission phase (9 with prednisolone treatment). Expression of CXC chemokine receptors (CXCRs) on leukocytes (including lymphocytes, monocytes, neutrophils) was measured using flow cytometry. RESULTS: Without prednisolone treatment, CXCR2 expression (on both total leukocytes and neutrophils) in relapsing phase was significantly higher than in remission-phase patients or normal individuals. By contrast, no significant difference was detected in the expression of CXCR1 between any ofthe groups. Importantly, low-dose prednisolone therapy reduced CXCR2 expression on neutrophils. CONCLUSIONS: CXCR2 has a potential role in promot-ing uveitis during ocular attack and might also be a useful marker for disease activity.

Adult↗
PubMed2005

Cellular events in the normal and inflamed cornea.

PURPOSE: Although normal cornea is an avascular transparent structure, bone marrow (BM)-derived cells exist in situ even in noninflamed conditions. We evaluated constitutive cellular trafficking into the cornea in the naive state and investigated how corneal inflammation may be initiated by various stimuli. METHODS: BM chimeric mice were generated using BM from enhanced green fluorescent protein (eGFP) transgenic mice. Corneas of chimeric mice were carefully studied by fluorescent biomicroscopy until 6 months after transplantation. To analyze initiation of cellular events in corneal immune response, we cauterized the center of the cornea or inoculated IL-1 beta into the corneal micropocket. Cellular events were analyzed by flow cytometry. RESULTS: At 2 weeks after BM transplantation, GFP cells gradually migrated into the cornea from the limbal area and were distributed over the entire cornea at 6 months. In both the cauterization and micropocket assays, infiltration of neutrophils and macrophages occurred on days 2 and 4, respectively. Depletion of neutrophils by anti-Gr-1 Ab significantly reduced corneal edema/opacity induced by cauterization. IL-1 beta-induced angiogenesis was markedly reduced in monocyte chemoattractant protein-1 knockout mice. CONCLUSIONS: BM-derived cells are recruited into the normal cornea and may be essential to maintain corneal clarity. In the inflamed cornea, neutrophils might be responsible for acute corneal edema/opacity and macrophages for corneal angiogenesis and chronic inflammation.

Animals↗
PubMed2005

The analysis of systemic tolerance elicited by antigen inoculation into the vitreous cavity: vitreous cavity-associated immune deviation.

The immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber-associated immune deviation (ACAID). We have investigated the mechanisms by which ocular inflammation associated with the vitreous cavity (VC) is reduced, by injecting either ovalbumin (OVA) or allogeneic splenocytes into the VCs of mice, and assessed the effect of this on delayed type hypersensitivity (DTH) responses. After antigen inoculation into the VC, antigen-specific DTH responses were significantly impaired and we named this phenomenon 'vitreous cavity-associated immune deviation' (VCAID). VCAID could also be induced by inoculating antigen-pulsed macrophages into the VC. However, VCAID did not develop either in mice with inflamed eyes, whether as a result of experimental autoimmune uveitis or coadministration of interleukin (IL)-6 in the VC, or in knockout mice deficient for natural killer T (NKT) cells. Finally, we found that so-called 'hyalocytes' are the only cells present in the VCs of normal mice, uniformly distributed on the retinal surface. Interestingly, they express F4/80, suggesting that hyalocytes are candidate antigen-presenting cells (APCs) responsible for mediating VCAID. As for the anterior chamber model, systemic tolerance can be induced in the VC in non-inflamed eyes and in the presence of invariant NKT cells.

Animals↗
PubMed2005

[The immunoregulatory role of local antigen-presenting cells in ocular inflammation].

The immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber-associated immune deviation (ACAID). We have recently shoun that the vitreous cavity(VC) also had the ability to induce tolerance and named this phenomenon 'vitreous cavity-associated immune deviation(VCAID). Ocular antigen-presenting cells(APCs) are known to be critical in inducing both ACAID and VCAID. In contrast to normal conditions, an inflamed eye no longer supports either ACAID or VCAID induction. We therefore elucidated the mechanism for terminating already established ocular inflammation. Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages produce various cytokines/chemokines and damage tissue in EAU. We found that only the macrophage-enriched cells from the eye produced RANTES(regulated upon activation normal T cells expressed and secreted) Neutralization of RANTES by specific antibodies in vivo exacerbated EAU. We also found that the ratio of ocular CD 4/CD 8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. Our data provide insight into the immunoregulatory role of macrophages mediated by RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines may cause local inflammation, since RANTES produced by ocular macrophages appears to suppress experimental autoimmune uveitis.

Animals↗
PubMed2004

Residual vitreous cortex after surgical posterior vitreous separation visualized by intravitreous triamcinolone acetonide.

OBJECTIVE: To visualize the residual vitreous cortex (VC) on the retinal surface after surgical posterior vitreous separation (PVS) during a pars plana vitrectomy (PPV), especially in patients with diabetic retinopathy. DESIGN: Case-control study. PARTICIPANTS: Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and rhegmatogenous retinal detachment (RRD). METHODS: A triamcinolone acetonide (TA)-assisted vitrectomy was performed on patients with the following diseases: PDR (40 eyes), DME (26 eyes), BRVO (11 eyes), and RRD (17 eyes). Eyes with no apparent preoperative posterior vitreous detachment were enrolled in this study. After performance of surgical PVS, the residual VC was visualized as a white gel highlighted by TA. Based on this finding, the residual VC pattern was then divided into 3 groups: (1) diffuse type (VC was diffusely present in the temporal vascular arcade), (2) focal type (a small island of VC was left), and (3) no residual VC. A multivariate analysis using analysis of variance was performed regarding the residual VC pattern, disease type, age, and the 3 different surgeons. MAIN OUTCOME MEASURES: Each surgeon determined the type of residual VC during the operation, and the results were confirmed by a postoperative review of the videotape records judged by the other 2 surgeons. RESULTS: Eighty percent of the PDR eyes demonstrated the diffuse type; 10%, the focal type; and 10%, no residual VC. Fifty-eight percent of the eyes with DME demonstrated the diffuse type; 19%, the focal type; and 23%, no residual VC. Eighteen percent of the BRVO eyes showed the diffuse type; 24%, the focal type; and 59%, no residual VC. Thirty percent of the RRD eyes showed the diffuse type; 30%, the focal type; and 40%, no residual VC. A multivariate logistic regression analysis showed that PDR was a predictor of the diffuse type of residual VC in comparison to RRD (odds ratio = 8.42, 95% confidence interval = 2.07-34.3). Neither age nor the surgeon was a significant factor for a specific type of residual VC. CONCLUSIONS: Diabetic eyes more often demonstrated the diffuse type of residual VC, even after surgical PVS. This information may be valuable for surgeons performing a PPV on patients with diabetic retinopathy.

Aged↗
PubMed2004

Two patients with severe corneal disease in KID syndrome.

PURPOSE: To report two independent Japanese patients with keratitis, ichthyosis, and deafness (KID) syndrome and severe corneal disorder. DESIGN: Observational case reports. METHODS: Clinical observation of a 5-year-old boy (Patient 1) and a 64-year-old man (Patient 2) with KID syndrome, presenting prominent corneal diseases. Molecular genetic assessment of the GJB2 gene encoding connexin-26 was performed. RESULTS: Patient 1 had bilateral diffuse superficial punctuate keratopathy with severe corneal neovascularization. He had a missense mutation of the GJB2 gene. Patient 2 had bilateral corneal stromal keratitis and right corneal ulceration with rupture of the Descemet membrane. He did not have any pathologic mutation of the GJB2 gene. The area of palisades of Vogt was diminished and tear production reduced in both patients. Topical eye drops, and corticosteroid or antibiotics, respectively, relieved them effectively. CONCLUSION: The impaired ocular surface regulating system might be a cause of corneal disease in KID syndrome and it can be treated by eye drops.

Anti-Bacterial Agents↗
PubMed2004

Abnormal retinal vascular development in IL-18 knockout mice.

Recent studies have indicated that interleukin 18 (IL-18) might act as either an angiogenic or an angiostatic factor, but the true function of this protein in vascular development is unclear. We therefore investigated the role of IL-18 in the formation of retinal vessels. Development of the retinal vasculature was compared in IL-18 knockout (KO) and wild-type (WT) mice at several different time points. The formation of vessels was evaluated using angiography of flat-mounted retinal samples after inoculation with fluorescein dextran. Retinal samples from both groups were also evaluated through histological examinations, and the expression of angiogenic factors was examined using the reverse-transcription-polymerase chain reaction. The capillary retinal vessels in both WT and IL-18 KO mice had reached the peripheral retina by postnatal day (P) 7. However, IL-18 KO mice showed angiectasis and vascular leakage at P7, especially in the mid-peripheral retina. These symptoms were not observed in WT mice at any stage. Histopathological analysis confirmed abnormal vascular formation in IL-18 KO mice at P14. Interestingly, these abnormalities regressed over time and had disappeared by P84. Several angiogenesis-associated factors, including vascular endothelial growth factor (VEGF), basic fibroblast-growth factor (bFGF), platelet-derived growth factor (PDGF) and pigment epithelium-derived factor (PEDF), were overexpressed in the retinas of IL-18 KO mice compared with those of WT mice at P14. Interferon-gamma was detected only in WT mouse retinas at P14. These results provide new evidence for the role of IL-18 in retinal vascular development.

Angiogenic Proteins↗
PubMed2003

Immunoregulatory role of ocular macrophages: the macrophages produce RANTES to suppress experimental autoimmune uveitis.

Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages play a crucial role in the generation of tissue damage in EAU. In fact, several chemokines are actually produced in the inflamed eye. The aim of this study was to elucidate the role of ocular macrophage-derived chemokines in EAU. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20, and the EAU severity was scored at multiple time points based on microscopic fundus observations (retinal vascular dilatation and exudates) and histological examinations. The peak inflammatory response was observed 1 wk (day 16) after the beginning of macrophage infiltration to the eye (day 9). Ocular-infiltrating cells were enriched or depleted of macrophages by magnetic beads and analyzed by real-time RT-PCR for chemokine mRNA production. We found that only the macrophage-enriched cells from the eye produced RANTES, and thus proposed that macrophage-derived RANTES facilitated the ocular inflammations. In contrast to our postulate, neutralization of RANTES by specific Ab in vivo on days 9 and 13 exacerbated EAU. We also found that the ratio of ocular CD4/CD8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. In conclusion, our data provide insight into the immunoregulatory role of macrophages and RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines cause local inflammation, since RANTES produced by ocular macrophages appears to suppress EAU.

Adjuvants, Immunologic↗
PubMed2003

CD4+ NKT cells, but not conventional CD4+ T cells, are required to generate efferent CD8+ T regulatory cells following antigen inoculation in an immune-privileged site.

Following inoculation of Ag into the anterior chamber (a.c.), systemic tolerance develops that is mediated in part by Ag-specific efferent CD8(+) T regulatory (Tr) cells. This model of tolerance is called a.c.-associated immune deviation. The generation of the efferent CD8(+) Tr cell in a.c.-associated immune deviation is dependent on IL-10-producing, CD1d-restricted, invariant Valpha14(+) NKT (iNKT) cells. The iNKT cell subpopulations are either CD4(+) or CD4(-)CD8(-) double negative. This report identifies the subpopulation of iNKT cells that is important for induction of the efferent Tr cell. Because MHC class II(-/-) (class II(-/-)) mice generate efferent Tr cells following a.c. inoculation, we conclude that conventional CD4(+) T cells are not needed for the development of efferent CD8(+) T cells. Furthermore, Ab depletion of CD4(+) cells in both wild-type mice (remove both conventional and CD4(+) NKT cells) and class II(-/-) mice (remove CD4(+) NKT cells) abrogated the generation of Tr cells. We conclude that CD4(+) NKT cells, but not the class II molecule or conventional CD4(+) T cells, are required for generation of efferent CD8(+) Tr cells following Ag introduction into the eye. Understanding the mechanisms that lead to the generation of efferent CD8(+) Tr cells may lead to novel immunotherapy for immune inflammatory diseases.

Animals↗
PubMed2003

Clearance of apoptotic photoreceptors: elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin alphavbeta3.

The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin alphavbeta3 revealed that phagocytotic clearance involves the PSR as well as integrin alphavbeta3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space.

Animals↗
PubMed2003

The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization.

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.

Animals↗
PubMed2002

Long-term survival of corneal allografts is dependent on intact CD1d-reactive NKT cells.

BALB/c mice that tolerate the allogeneic grafts develop allogeneic-specific anterior chamber-associated immune deviation. Because CD1d-reactive NKT cells are essential for anterior chamber-associated immune deviation, we postulated that the survival of C57BL/6 (B6) cornea graft in BALB/c mice was also dependent on CD1d-reactive NKT cells. The B6 corneal graft rejection rate in BALB/c vs Jalpha281 knockout (KO) mice, which lack NKT cells, was measured. While there were no difference in the early phase of rejection, the survival rates at 12 wk after grafting for BALB/c and Jalpha281 KO mice were 50 and 0%, respectively. Because anti-CD1d mAb abrogated the corneal graft survival in the wild-type mice we concluded that CD1d-reactive NKT cells were essential for graft survival. Moreover, allospecific T regulatory (Tr) cells correlated with acceptance of B6 grafts in BALB/c mice, and the adoptive transfer of these allospecific Tr cells to Jalpha281 KO mice allowed a 50% survival rate of B6 cornea grafts. In conclusion, CD1d-reactive NKT cells are required for induction of allospecific Tr cells and are essential for survival of corneal allografts. Mechanisms that contribute to cornea graft acceptance may lead to new therapies for improvement in graft survival in high-risk corneas and other transplanted tissues and grafts.

Adoptive Transfer↗
PubMed2002

CD1d on antigen-transporting APC and splenic marginal zone B cells promotes NKT cell-dependent tolerance.

CD1d-reactive NKT cells are required for the development of antigen-specific T regulatory (Tr) cells responsible for mediating systemic tolerance induced through an immune privileged site such as the eye. The aim of this study was to elucidate the cellular source of CD1d needed for NKT cell activation. Transforming growth factor beta (TGF beta)-2-treated peritoneal exudate cells (PEC) functionally resemble "eye-derived" antigen-presenting cells (APC) and contribute to the generation of Tr cells both in vitro and in vivo. However, when TGF beta-2-treated PEC were pretreated with CD1d-specific antibodies or lacked CD1d expression they failed to induce Tr cells. In addition, we show that the subpopulation of marginal zone (MZ) B cells within the spleen is necessary for induction of Tr cells and that they also must express CD1d. The role of MZ B in tolerance is novel and previously unexplored. Thus, CD1d is necessarily expressed on putative eye-derived APC and splenic MZ B cells for efficient generation of Tr cells in CD1d-reactive NKT cell-dependent tolerance.

Adoptive Transfer↗