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Biomedical subjects

Hajime Shinoda

Publications and source records attributed to Hajime Shinoda.

11 recordsLinked to original sources
PubMed2007

Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovascularization.

PURPOSE: Recently, it was revealed that the inhibition of nonproteolytic activation of prorenin led to significant suppression of ocular inflammation in endotoxin-induced uveitis. The purpose of the present study was to investigate whether nonproteolytically activated prorenin plays a role in ischemia-induced retinal neovascularization. METHODS: C57BL/6 neonatal mice were reared in an 80% concentration of oxygen from postnatal (P) day 7 to P12, followed by room-air breathing to P17 to induce ischemia-initiated retinal neovascularization. Tissue localization of activated prorenin and prorenin receptor was examined by immunohistochemistry. Animals received intraperitoneal injections of handle-region peptide (HRP), a decoy peptide corresponding to the handle region of prorenin, which inhibits prorenin receptor-mediated upregulation of the renin-angiotensin system (RAS). A concanavalin A lectin perfusion-labeling technique was used to evaluate the areas of physiologic and pathologic retinal new vessels and the number of leukocytes adhering to the vasculature. Retinal mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA. RESULTS: Retinal vessels in ischemic retinopathy eyes were positive for activated prorenin and prorenin receptor. Pathologic, but not physiologic, retinal neovascularization was significantly attenuated in HRP-treated mice compared with vehicle- or control peptide-treated animals. The number of adherent leukocytes was also significantly reduced. Retinal mRNA expression and protein levels of ICAM-1, VEGF, VEGFR-1, and VEGFR-2 in ischemic retinopathy were also significantly suppressed by the application of HRP. CONCLUSIONS: The present findings suggest that nonproteolytic activation of prorenin selectively promotes pathologic, but not physiologic, retinal neovascularization through the inflammatory processes related to pathologic neovascularization.

Animals↗
PubMed2006

Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.

PURPOSE: A recent study revealed that angiotensin receptor signaling mediates ocular inflammation and neovascularization. It was also found that prorenin undergoes nonproteolytic activation leading to upregulation of the renin-angiotensin system (RAS) when prorenin receptor interacts specifically with the handle region of prorenin. The purpose of the present study was to elucidate the role of the receptor-dependent nonproteolytic activation of prorenin in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in Long-Evans rats by a single intraperitoneal injection of 100 microg lipopolysaccharide (LPS). Tissue localization of total prorenin, prorenin receptor, and activated prorenin in the EIU retina was examined by immunohistochemistry. To inhibit the prorenin receptor-mediated upregulation of the RAS, a decoy handle-region peptide (HRP) was intraperitoneally administered 24 hours before and immediately after the injection of LPS. Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. In addition, leukocyte infiltration into the vitreous cavity and protein concentration in the anterior chamber were also measured. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, and C-C chemokine ligand (CCL) 2/monocyte chemotactic protein (MCP)-1 were examined by RT-PCR and ELISA. RESULTS: Retinal vessels in rats with EIU were strongly positive for total prorenin, prorenin receptor, and activated prorenin. Systemic treatment with HRP resulted in dose- and time-dependent inhibition of the leukocyte adhesion and infiltration and the protein leakage, all of which were increased by the induction of EIU. Retinal mRNA expression and protein levels of ICAM-1, CCL2/MCP-1 and IL-6, induced in rats with EIU, were also significantly suppressed with application of HRP. CONCLUSIONS: These findings demonstrate for the first time that nonproteolytically activated prorenin plays a significant role in the development of ocular inflammation in the EIU model. The present study suggests the potential use of HRP, a decoy peptide binding to the prorenin receptor, as a therapeutic agent to reduce ocular inflammation.

Animals↗
PubMed2005

Selective suppression of pathologic, but not physiologic, retinal neovascularization by blocking the angiotensin II type 1 receptor.

PURPOSE: To investigate the anti-inflammatory and anti-angiogenic effects of telmisartan, an angiotensin II type 1 receptor (AT1-R) antagonist, on ischemia-induced retinal neovascularization. METHODS: C57BL/6 neonatal mice were reared in an 80% concentration of oxygen from postnatal day (P)7 to P12, followed by room-air breathing until P17, to induce ischemia-initiated retinal neovascularization (i.e., a murine model of ischemic retinopathy). Tissue localization of AT1-R was examined by immunohistochemistry for murine retinal wholemounts and human fibrovascular tissues excised at vitrectomy for proliferative diabetic retinopathy. Animals received intraperitoneal injection of telmisartan or vehicle. A concanavalin A lectin perfusion-labeling technique was used to evaluate the areas of physiological and pathologic retinal new vessels and the number of leukocytes adhering to the vasculature. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA. RESULTS: Vessels in human fibrovascular tissues and the murine retinas were positive for AT1-R. Pathologic (P < 0.01), but not physiologic (P > 0.05), retinal neovascularization was significantly suppressed in telmisartan-treated mice compared with vehicle-treated animals. The number of adherent leukocytes (P < 0.01) was also significantly reduced, together with retinal ICAM-1 levels (P < 0.01) in the telmisartan-treated group compared with the control group. No significant difference was detected in retinal VEGFR-2 levels between the two groups, whereas retinal VEGFR-1 levels in the telmisartan-treated group were significantly (P < 0.05) lower than in the vehicle-treated group. CONCLUSIONS: The present findings suggest that the AT1-R signaling blockade leads to the selective suppression of pathologic, but not physiological, retinal neovascularization through the inhibition of the inflammatory processes related to pathologic neovascularization.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor.

PURPOSE: To examine whether the angiotensin II type 1 receptor (AT1-R) signaling plays a role in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in C57BL/6 mice by a single intraperitoneal injection of 150 mug lipopolysaccharide (LPS). Tissue localization, mRNA expression, and protein levels of AT1-R in murine retinas were examined by immunohistochemistry, RT-PCR, and Western blot analyses, respectively. Telmisartan, an AT1-R antagonist widely used as an antihypertensive agent, was administered intraperitoneally at a dose of 10 mg/kg daily for 5 days until the injection of LPS. Twenty-four hours after administration, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1 were examined by RT-PCR and ELISA, respectively. Protein concentration and inflammatory cells in the aqueous humor were also measured. RESULTS: Retinal vessels were positive for AT1-R. In mice with EIU, retinal AT1-R mRNA and protein levels were significantly increased when compared to the normal control. EIU animals also showed significant increases in the number of inflammatory cells infiltrating the anterior chamber and adhering to the retinal vessels and in retinal ICAM-1 levels. Administration of telmisartan to EIU mice resulted in significant suppression of retinal ICAM-1 expression and leukocyte adhesion and infiltration compared with vehicle treatment. Protein concentration in the aqueous humor of telmisartan-treated EIU mice tended to be lower than that of vehicle-treated EIU mice, but the difference was not statistically significant. CONCLUSIONS: AT1-R signaling blockade inhibited retinal ICAM-1 upregulation and leukocyte adhesion and infiltration in the EIU model. These results suggest the potential use of an AT1-R antagonist as a therapeutic agent to reduce ocular inflammation.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Hypoxia induces the expression of membrane-type 1 matrix metalloproteinase in retinal glial cells.

PURPOSE: Fibrovascular tissue formation in diabetic retinopathy necessitates not only angiogenic activity but also proteolytic activity, which is at least in part attributable to the induction of membrane-type 1 matrix metalloproteinase (MT1-MMP) in retinal glial cells. However, little is known about the triggers for MT1-MMP induction in the diabetic retina. In the present study, the effect of tissue hypoxia on MT1-MMP expression in retinal glial cells was investigated. METHODS: Retinal glial cells were isolated from the rabbit retina and cultured under either normoxic (20% O(2)) or hypoxic (1% O(2)) conditions in the presence or absence of the inhibitor for vascular endothelial growth factor (VEGF) receptor signal transduction or a neutralizing antibody against VEGF. The expression level of MT1-MMP in retinal glial cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, Western blot analysis and immunocytochemistry. Expression of VEGF and VEGF receptors, VEGFR-1 and VEGFR-2, was also examined by RT-PCR. RESULTS: RT-PCR and real-time PCR analyses showed a 2.3-fold induction of MT1-MMP expression in retinal glial cells under hypoxic conditions. VEGF, especially its isoform VEGF(165), and VEGFR-2 were also upregulated in retinal glial cells by hypoxia, and hypoxia-induced MT1-MMP expression was inhibited in the presence of the VEGFR-2 inhibitor SU1498 or the anti-VEGF antibody. CONCLUSIONS: Hypoxia can induce MT1-MMP expression in retinal glial cells, and the hypoxia-induced expression of MT1-MMP is mediated by VEGF in an autocrine fashion.

Animals↗
PubMed2004

A clinicopathologic case report on macular hole associated with von Hippel-Lindau disease: a novel ultrastructural finding of wormlike, wavy tangles of filaments.

BACKGROUND: We describe a novel ultrastructural finding observed in an epiretinal membrane excised from a patient with von Hippel-Lindau disease. METHODS: This interventional case report presents a 45-year-old woman who noted decreased vision in her right eye and was referred for treatment of a macular hole secondary to von Hippel-Lindau disease. Blindness had occurred previously in the left eye because of exudative retinal detachment. Funduscopic examination revealed a macular hole associated with a delicate epiretinal membrane, multiple retinal angiomas, and multiple old laser scars. Vitrectomy was performed in her right eye. The epiretinal membrane was peeled off and processed for light and electron microscopy. RESULTS: Postoperatively the macular hole was successfully closed, and vision recovered to 20/20 from 20/40. In the excised epiretinal membrane, flattened glial cells and extracellular matrix containing fibrous elements formed a multilayered pattern. Ultrastructurally, the fibrous elements appeared as wormlike, wavy tangles of filaments (WWTF) with an orientation parallel to the surface of the epiretinal membrane. Just above the WWTF, flattened glial cells frequently extended thin cytoplasmic processes with pinocytotic vesicles. CONCLUSION: The ultrastructure suggested that retinal glial cells had induced a remodeling of the collagenous stroma in the posterior vitreous cortex, resulting in tangential macular traction.

Basement Membrane↗
PubMed2004

Successful treatment of subfoveal choroidal neovascularization associated with combined hamartoma of the retina and retinal pigment epithelium.

PURPOSE: To describe a patient with subfoveal choroidal neovascularization (CNV) associated with combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), treated successfully by submacular surgery. DESIGN: Interventional case report. METHODS: A 12-year-old girl was referred to our clinic for evaluation. Visual acuity was 20/30 in the affected left eye. Ophthalmoscopy disclosed juxtapapillary CHRRPE and subfoveal pigmented CNV. Vitreous surgery was carried out because of visual deterioration to 20/60. RESULTS: The posterior vitreous was strongly attached to glial tissue at the superior margin of the optic disk in the CHRRPE region. The CNV, which was not connected with the CHRRPE, was carefully removed, resulting in visual improvement to 20/20 5 months after surgery. Histologically, the excised membrane showed fibroblast-rich cellular component and a type 2 configuration. CONCLUSION: Submacular surgery can be effective for the treatment of secondary CNV associated with CHRRPE.

Child↗
PubMed2004

[Intravitreal injection of triamcinolone acetonide for cystoid macular edema resistant to vitreous surgery].

PURPOSE: To report the efficacy of intravitreal injection of triamcinolone acetonide(TA) for cystoid macular edema remaining after vitreous surgery. METHODS: Eight eyes of 7 patients aged from 32 to 84 years old were studied. The original diseases that caused macular edema were central retinal vein occlusion in 2 eyes, branch retinal vein occlusion in one eye, Irvine-Gass syndrome in 2 eyes, and diabetic retinopathy in 3 eyes. 4 mg of TA was injected intravitreally and visual acuity and foveal thickness measured by optical coherence tomography(OCT) were evaluated in before and after the surgery. RESULTS: Macular edema resolved rapidly after injection of TA in all cases and cysts were extinguished or diminished. The foveal thickness in OCT was reduced significantly from preoperative 495 +/- 116 (mean +/- standard deviation) microns to 267 +/- 117 microns after one week, and 246 +/- 81 microns after one month. The effect persisted for three months. Visual improvement of more than two Snellen lines was seen in 4 eyes. No side effects were observed except a temporary increase of intraocular pressure in one eye. CONCLUSION: Intravitreal injection of TA is effective in a short-term for cystoid macular edema remaining after vitrectomy.

Adult↗