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Biomedical subjects

H Inomata

Publications and source records attributed to H Inomata.

At least 73 records · Page 4Linked to original sources
PubMed1996

The temporal and spatial vascular endothelial growth factor expression in retinal vasculogenesis of rat neonates.

Vascular endothelial growth factor (VEGF) has been identified as an endothelial cell-specific mitogen with potent angiogenic properties. VEGF is overexpressed in pathologic angiogenesis observed in tumor growth, rheumatoid arthritis, and retinal angiogenic diseases such as diabetic retinopathy and retinopathy of prematurity. VEGF expression in physiologic angiogenesis, i.e., vasculogenesis, has also been reported in the embryonic organs such as brain, kidney, spleen, and lung. However, the details of VEGF expression in vasculogenesis remain largely unclear. To determine if VEGF contributes to vasculogenesis in the developing tissues, VEGF expression was studied by both immunohistochemistry and in situ hybridization in newborn rat retinas on postnatal days 3, 7, 14, and 30. Vasculogenesis was assessed by both the ink perfusion method and a histologic examination. To identify the cell types of VEGF-expressing cells, immunohistochemistry for cell markers such as glial fibrillary acidic protein and von Willebrand factor was performed. On postnatal days 3 and 7, when retinal vasculogenesis was active, VEGF mRNA and protein(s) were prominently expressed in the ganglion cell and the inner nuclear layers. In rats, as well as humans, these two layers are where the retinal vessels develop, and these two layers depend solely on the retinal vessels. In addition to the ganglion and the inner nuclear layers, VEGF protein(s) were located in the endothelial cells of the developing vessels and the angioblasts, i.e., endothelial precursors. On postnatal day 14, when vasculogenesis became inactive, VEGF mRNA expression markedly decreased. These results indicated that VEGF expression in the developing retinas is temporally and spatially correlated with retinal vasculogenesis.

Animals↗
PubMed1996

The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas.

In the retinas of streptozotocin-induced diabetic rats, the relationship between the expression of vascular endothelial growth factor (VEGF) and the breakdown of the blood-retinal barrier (BRB) was investigated. VEGF mRNA expression was examined by in situ hybridization and VEGF protein expression was examined by immunohistochemistry. BRB breakdown was immunohistochemically demonstrated by detecting extravasation of albumin. In diabetic retinas, VEGF mRNA was expressed by the following cells: (a) ganglion cells, (b) glial cells such as astrocytes and Muller cells, whose cell processes are closely associated with retinal vessels, (c) smooth muscle cells and pericytes in the vessel walls, and (d) the retinal pigment epithelium. In diabetic retinas, BRB breakdown was immunohistochemically detected, and VEGF protein expression was markedly increased in comparison to that in the control retinas. The rates of both BRB breakdown and VEGF immunoreactivity increased in proportion to the duration of diabetes. In addition, the rate of BRB breakdown was much higher in vessels with VEGF immunoreactivity than in vessels without VEGF immunoreactivity. These findings indicate that VEGF has a major promoting effect on BRB breakdown in simple diabetic retinopathy. VEGF immunoreactivity was distributed throughout all layers of the retinas, and were most prominently observed in the nerve fiber layer, especially near the optic disc and around large vessels. These two regions coincide with the sites wherein BRB breakdown is clinically detected by fluorescein angiography in diabetic patients. Neovascularization in proliferative diabetic retinopathy is also most commonly observed in these two regions. Because VEGF promotes endothelial proliferation, these findings suggest that VEGF plays a role in the budding of retinal neovascularization and, as a result, could induce proliferative diabetic retinopathy.

Animals↗
PubMed1996

[Inhibitory effect of vitamin E succinate on the proliferation of cultured bovine choroidal endothelial cells].

We report the effect of vitamin E succinate (VE succinate) on the proliferation of cultured bovine choroidal endothelial cells (BCECs). BCECs were incubated with a medium containing vitamin E (VE) or one of the VE derivatives gamma-tocopherol, VE phosphate, VE succinate, VE nicotinate, VE acetate, or trolox, at a concentration of 10 microM. The proliferation of BCECs was assessed by 3H-thymidine uptake and cell counting. Especially in VE and VE succinate, the proliferation assay was performed on BCECs at two different stages, that is, the proliferating stage and the quiescent stage. The effect of protein kinase C (PKC) stimulator phorbol ester (PMA) on the VE succinate-induced inhibition of BCEC proliferation was also examined. VE succinate was found to significantly inhibit BCEC proliferation at a concentration of 10 microM or greater both by 3H-thymidine uptake assay and by cell counting. This inhibitory effect was not noted in other VE derivatives. The inhibitory effect was the most prominent in the proliferating BCECs and co culture of PMA. VE succinate inhibits the proliferation of cultured BCECs and PKC is involved in this action at least in part.

Animals↗
PubMed1996

Differential effects of diltiazem and nitroglycerin on cytosolic Ca2+ concentration and on force in the bovine ophthalmic artery.

PURPOSE: To determine the mechanisms of inhibition by diltiazem (Dil) and nitroglycerin (NG) of the contraction induced by serotonin (5-HT) in the ophthalmic artery. METHODS: Using front-surface fluorometry of fura-2 and the medial strips of the bovine ophthalmic artery, [Ca2+]i and force were monitored simultaneously. Changes in the force at a constant [Ca2+]i were determined by use of receptor-coupled membrane permeabilization with alpha-toxin. RESULTS: In the presence of extracellular Ca2+, 5-HT (10(-5) M) induced an initial transient and subsequently lower steady state elevation of [Ca2+]i. The transient elevation of [Ca2+]i was dependent on both intracellular and extracellular [Ca2+]i, whereas the steady state elevation was dependent on only extracellular Ca2+. For a given level of elevation of [Ca2+]i, 5-HT produced a greater force than the depolarization with high external K+ (118 mM) solution. In the permeabilized ophthalmic artery smooth muscle, 5-HT enhanced the contractile response to constant cytosolic Ca2+ (pCa 6.5) in the presence of guanosine triphosphate (GTP, 10 microM), but not in its absence. Therefore, 5-HT induces [Ca2+]i elevation, depending on both extracellular (Ca2+ influx) and intracellular Ca2+ (Ca2+ release), and it potentiates the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins. 5-HT-induced release of Ca2+ from the store was inhibited by NG, but not by Dil, in a concentration-dependent manner. However, neither NG nor Dil inhibited caffeine (20 mM)-induced release of Ca2+ from the store. Dil (10 microM) and NG (10 microM) inhibited in a concentration-dependent manner the steady state elevations of [Ca2+]i (Ca2+ influx) and force induced by 5-HT (10 microM) in the presence of extracellular Ca2+. Dil equally inhibited the steady state elevations of [Ca2+]i and force induced by 5-HT, whereas NG inhibited the force to a greater extent than expected from the reduction in [Ca2+]i. In the permeabilized ophthalmic artery smooth muscle, NG (10 microM), but not Dil (10 microM), decreased the force development induced by GTP (10 microM) and 5-HT (10 microM) at constant [Ca2+]i (pCa 6.5). These results indicate that NG, but not Dil, decreases the Ca2+ sensitivity of contractile apparatus. CONCLUSIONS: The authors found that 5-HT contracts the ophthalmic artery smooth muscle by the elevation of [Ca2+]i mediated by the release of intracellular Ca2+ and the influx of extracellular Ca2+, as well as by an increase in the Ca2+ sensitivity of the contractile apparatus through the activation of G-proteins, and that Dil relaxes 5-HT-mediated contraction of ophthalmic artery primarily by inhibiting the Ca2+ influx and, hence, by decreasing [Ca2+]i without having any effect on the Ca2+ sensitivity of the contractile apparatus. Nitroglycerin relaxes the ophthalmic artery not only by decreasing [Ca2+]i (inhibition of both the Ca2+ release and Ca2+ influx) but also by decreasing the Ca2+ sensitivity of the contractile apparatus.

Animals↗
PubMed1996

Distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma.

We investigated histo-chemically the composition and distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma. Cupromeronic blue in combination with a series of enzyme digestions and nitrous acid treatment were used. The spaces between the trabecular beams were lined by a single layer of vascular endothelium and were filled with red blood cells. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. Chondroitin-sulfate- and dermatan-sulfate-type proteoglycans were present in association with collagen fibrils in the extracellular matrix. Heparan-sulfate-type proteoglycans were present in association with the basal lamina of both the vascular endothelial cells and the trabecular cells. It is unlikely that these abnormalities in the type or distribution of proteoglycans in the trabecular meshwork have a major role in the pathogenesis of glaucoma.

Adult↗
PubMed1995

High D-glucose stimulates the cell cycle from the G1 to the S and M phases, but has no competent effect on the G0 phase, in vascular smooth muscle cells.

The effects of high (28mM) D-glucose (HG) on the cell cycle progression were investigated in rat aorta vascular smooth muscle cells (VSMCs) in primary culture, using an immunocytochemical analysis of cell-cycle-specific nuclear antigens. HG had no effect on the cell cycle of the serum-deprived G0 cells, whereas platelet-derived growth factor (PDGF) stimulated the entry of the G0 cells to the G1 phase without a further progression to the S and M phases. HG, but neither mannitol nor L-glucose, stimulated the progression of the PDGF-pretreated G1 cells to the S and M phases, which was blocked by calphostin-C, a protein kinase C (PKC) blocker. HG did not affect the cytosolic Ca2+ concentration ([Ca2+]i). These data suggest that HG has no competent effect on the G0 cells and acts as a progression growth factor (to stimulate the cell cycle from the G1 to the S/M) in VSMCs through the mechanism, which may be insensitive to [Ca2+]i and mediated by PKC.

Animals↗
PubMed1995

Pericytes of newly formed vessels in experimental subretinal neovascularization.

OBJECTIVE: To examine the role of pericytes in the progression of subretinal neovascularization in a primate model. METHODS: Subretinal neovascularization was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 3, 7, 14, and 21 days after photocoagulation and were studied with light and electron microscopy. RESULTS: Three days after photocoagulation, newly formed vessels were observed in the choroid and subretinal space. Although most of these vessels had an immature appearance and consisted only of endothelial cells that formed narrow lumens, mitotic figures of pericytes were occasionally found near the endothelial cells. Seven days after photocoagulation, all of the newly formed vessels possessed pericytes. Fourteen days after photocoagulation, many vessels appeared to be mature. Many sites of pericyte-endothelial cell contact were observed. These contacts were composed of cytoplasmic interdigitation and membrane apposition. By 21 days after photocoagulation, the mature vessels had increased in number, and the endothelial cells had many fenestrations with diaphragms. The pericyte coverage of the endothelial cells was less at this stage than at 14 days after photocoagulation, and sites of pericyte-endothelial cell contacts were observed only rarely. CONCLUSION: Pericytes are involved in maturation of the endothelial cells that form subretinal new vessels.

Animals↗
PubMed1995

Epiretinal membrane formation. Light and electron microscopic study in an experimental rabbit model.

OBJECTIVE: To clarify the role of retinal glial cells in epiretinal membrane formation. METHODS: We injected autologous whole blood into the vitreous cavity of albino rabbits and studied the events in the vitreoretinal interface at intervals during the course of 1 year by light and electron microscopy. RESULTS: Epiretinal membranes were first found 2 weeks after the treatment. At this stage, epiretinal membranes were composed of both glial cells and macrophages. Mitotic figures of glial cells were found in the retina. The nuclei of glial cells migrated, passing through the inner limiting membrane and onto the retinal surface. At 6 months, macrophages and red blood cells disappeared from the epiretinal membranes. The epiretinal membranes became thicker with time. Finally, these epiretinal membranes were composed solely of glial cells. CONCLUSIONS: At the early stage, macrophages participate with glial cells in epiretinal membrane formation; however, glial cells are the main constituent of epiretinal membranes during the late stage.

Animals↗
PubMed1995

Hypoxia-induced expression of vascular endothelial growth factor by retinal glial cells promotes in vitro angiogenesis.

To determine whether retinal glial cells (RGCs) participate in the paracrine regulation of retinal neovascularization, we investigated whether cultured RGCs synthesize and release vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) under normoxic or hypoxic conditions. Northern blot analysis demonstrated that cultured RGCs transcribed both VEGF mRNA with two molecular bands approximately 3.9 and 4.3 kilobases (kb), and bFGF mRNA with approximately 3.7 and 6.0 kb. The expression of VEGF mRNA was greatly enhanced by hypoxic cultivation (2% oxygen) when compared with normoxic cultivation (20% oxygen), while the expression of bFGF mRNA by RGCs was not significantly affected by hypoxia. The effects of RGCs-conditioned media (CM) on tritiated-thymidine incorporation and in vitro angiogenesis by retinal capillary endothelial cells (RECs) in producing the formation of capillary-like tubes in type I collagen gels, were evident in the observation that RGCs-CM harvested after hypoxic cultivation significantly enhanced tritiated-thymidine incorporation (1.9 times, P < 0.01) and in vitro angiogenesis (2.4 times, P < 0.01) compared with the normoxic RGCs-CM. These enhancing effects of RGCs-CM at hypoxia were suppressed by anti-VEGF neutralizing antibody. Furthermore, RECs were shown to express mRNA encoding the VEGF receptor flt-1 by northern blot analysis. These results suggest that VEGF expressed by RGCs under hypoxic conditions plays an integral role in the initiation and progression of retinal neovascularization in a paracrine manner.

Animals↗
PubMed1995

Prognostic factors of vision in patients with Behçet disease.

BACKGROUND: Behçet disease is a chronic, recurrent, inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. The etiology is unknown. Although many of these patients become blind, some have good vision all their life. METHODS: To attain more accurate data on the prognosis of these patients, the authors studied 52 Japanese patients (101 eyes) seen at Kyushu University Hospital between 1980 and 1990. At the first visit, patients ranged in age from 21 to 61 years; at onset, they ranged in age from 17 to 55 years; and the disease duration at first visit was from 0 to 22 years. Thirty-five of the 101 eyes had a visual loss of more than five lines or the patients became blind. The authors divided the subjects into two groups--favorable group and unfavorable group. If an eye had more than five lines of visual loss or the patient became blind 3 years after the first visit, it was placed in the unfavorable group, and if not, it was classed in the favorable group. Thirty-two factors determined from clinical records were used to select statistically significant risk factors for visual loss, using univariate analysis and multivariate logistic regression analysis. RESULTS: Univariate analysis showed the following four factors that were significantly different between favorable and unfavorable groups: sex, disease interval, other complications, and skin lesions (first year). Multivariate analysis showed that the following seven factors had mutually independent contributions to visual loss: skin lesions; arthritis; posterior attacks; other complications (experienced), including gastrointestinal, vascular, and central nervous system lesions; female sex; disease interval; and anterior attacks. The first four factors have effects of losing vision, whereas the others are related to vision retention. CONCLUSION: The authors find that skin lesions, arthritis, posterior attacks, and other complications are linked to loss of vision, whereas female sex, disease interval, and anterior attacks are related to retention of vision.

Adult↗
PubMed1995

Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels.

In rat diabetic retinas, we immunohistochemically looked for vascular endothelial growth factor (VEGF) which is also known as vascular permeability factor (VPF). In nondiabetic retinas, VEGF immunoreactivity was weak and restricted to the nerve fiber and ganglion cell layers. On the other hand, in diabetic retinas, VEGF immunoreactivity was markedly increased and was observed in all layers of the retina, especially in the perivascular area. Hyperpermeability of these vessels was confirmed by immunohistochemically detecting extravasation of albumin. These findings indicate that vascular endothelial growth factor plays an important role in blood-retinal barrier breakdown in diabetic retinopathy.

Actins↗
PubMed1995

Detection of proteoglycans in human posterior capsule opacification.

Using cuprolinic blue staining, we histochemically examined the ultrastructural localization of proteoglycans in the fibrous-type human posterior capsule opacification. This capsule opacification contained proteoglycans that showed positive staining with cuprolinic blue. Many cuprolinic-blue-positive filaments were present within the bundles of collagen fibrils, basal lamina-like material and basal lamina of proliferated lens epithelial cells. Pretreatment with enzymes and nitrous acid revealed that the collagen fibrils contained chondroitin sulfate and dermatan sulfate, whereas the basal lamina-like material and basal lamina of epithelial cells contained heparan sulfate. These results suggest that proteoglycans are one of the components in posterior capsule opacification.

Aged↗
PubMed1995

Detection of varicella-zoster virus genome having a PstI site in the ocular sample from a patient with acute retinal necrosis.

We detected the virus genome in ocular samples from a 65-year-old woman with clinically diagnosed acute retinal necrosis using DNA amplification. She exhibited occlusive retinal vasculitis, confluent necrotizing retinitis, mainly peripheral, and iridocyclitis. For DNA amplification, we used recently published primers specific for varicella-zoster virus (VZV) and herpes simplex virus. Using VZV primers, we detected the VZV genome in the aqueous humor, but not in the vitreous, by amplifying a DNA fragment 642 base pairs in length. HSV DNA was not detected. After detecting the VZV genome, PstI restriction endonuclease was used because an epidemiological study found that about 25% of the VZV strains in Japan carry a mutation lacking a PstI recognition site. The VZV genome from the patient had a PstI cleavage pattern, while the positive control had a VZV genome that carried a PstI-site-less mutation. We considered our patient with acute retinal necrosis to be infected with VZV having a PstI site.

Aged↗
PubMed1995

Tecogalan sodium inhibits corneal neovascularization induced by basic fibroblast growth factor.

The antiangiogenic effect of tecogalan sodium on corneal neovascularization was investigated. Tecogalan sodium, a sulfated polysaccharide peptidoglycan complex isolated from an Arthrobacter species, has been reported to inhibit angiogenesis induced by basic fibroblast growth factor (bFGF) as well as tumor angiogenesis related to Kaposi's sarcoma. Corneal neovascularization induced by bFGF was inhibited by tecogalan sodium in a dose-dependent manner. Since bFGF is known to have a promoting effect on corneal neovascularization, tecogalan sodium may be possible therapeutic agent for corneal neovascularization, which can cause severe visual disturbances.

Animals↗
PubMed1995

Proliferative vitreoretinopathy in Coats' disease. Clinicohistopathological case report.

We report the clinicohistopathological findings of the proliferative vitreoretinopathy in an eye with Coats' disease using the tissue obtained during surgery. A 28-year-old man, who had experienced poor vision in his right eye for a period of 4 years, was referred to our hospital. Examination revealed an extensive yellow exudate in the subretinal space and a tractional retinal detachment. Prominent teleangiectatic retinal vessels were also temporally present. Evident epiretinal membranes were present in the postequatorial area. We performed a scleral buckling, vitrectomy, membrane peeling, endophotocoagulation and silicone oil tamponade. A histological examination revealed that the epiretinal membrane consisted of collagen fibers, glial proliferation, foam cells and lymphocytes. The foam cell in the epiretinal membrane is a characteristic finding in an eye with Coats' disease.

Adult↗
PubMed1995

Relationship between intraocular pressure and age in the exfoliation syndrome.

We examined the presence or absence of exfoliative material and measured the intraocular pressure (IOP) of 220 residents of a nursing home. The prevalence of the exfoliation syndrome increased with age and the IOP of persons with the exfoliation syndrome was higher than that of persons without the syndrome. In eyes with the exfoliation syndrome, the IOP had a tendency to decrease with increasing age. Aging had little influence on IOP in eyes without the exfoliation syndrome. There were significant differences between the two groups with regard to the effects of aging on IOP.

Aged↗