Biomedical subjects
Publications and source records attributed to H Ohkuma.
A flexible aneurysm clip applier with a small spindle-shaped head was manufactured. It is useful for aneurysmal clipping through a narrow space and the clip can be set in various directions due to its flexibility.
Indocyanine green infrared fluorescence angiography (ICG angiography) was compared with the fluorescein angiography (FAG) to evaluate its benefit. Experimentally induced choroidal neovascularization (ChNV), by laser photocoagulation of monkey eyes was studied by means of cast preparation correlating with findings of ICG angiography. FAG could detect ChNV more clearly than ICG angiography. However, some (2/35 sites) ChNVs with subretinal hemorrhage could be detected only with ICG angiography. In the early phase, the densely distributed part or thick vessels of ChNV could be detected with ICG angiography. On the other hand, the loose part could not be detected. Cast preparation did not show morphologic difference between leaky and non-leaky lesions with ICG angiography. These results showed that ICG angiography could not produce clearer results than FAG. However, ChNVs covered with subretinal hemorrhage could be detected only with ICG angiography. ICG angiography has complementary value in conjunction with FAG in order to detect ChNVs.
Free radicals are thought to be one of the causes of retinal light damage. Experiments were performed to identify the production of free radicals in light exposed retinas of rabbits using nitro blue tetrazolium (NBT) staining. In addition, a free radical scavenger, alpha-tocopherol, was administered systemically before light exposure to evaluate the protective effect against the retinal light damage. Pigmented rabbits were exposed to xenon light without long waves for 60 minutes. The eyes were enucleated immediately after light exposure, and incubated in the equilibrated media at 37 degrees C with 0.1 mM NBT solution for 60 minutes. After incubation, the eyes were embedded in paraffin, sectioned, and mounted without further staining. The same procedure was done to the tocopherol treated retinas. In the light exposed eyes, the NBT staining was markedly observed at the inner retina, and the staining was more remarkable than that of the non-exposed eyes. The tocopherol treated eyes showed weaker NBT staining in the inner retina than the non-treated eyes. The results suggest that free radicals are increased in the inner retina by light exposure and alpha-tocopherol suppresses production of free radicals.
We studied the effect of human interferon-beta on reconstruction of the choriocapillaris following laser photocoagulation in monkey eyes. Moderate dye laser photocoagulation caused the occlusion of the choriocapillaris by the intraluminal thrombus in the photocoagulated lesions on the retina. After 3 days, immature endothelial cells began to migrate towards the center from the edge of the lesions. After 7 days capillaries were newly formed, and after 14 days the choriocapillaris in the lesions was almost reconstructed. Systemic administration of interferon-beta after photocoagulation suppressed the reconstruction of the choriocapillaris remarkably. These results suggest that interferon-beta inhibits proliferation and migration of the capillary endothelium on the retina. Interferon-beta may be effective as medication for the treatment of age-related macular degeneration.
We studied histologically the effect of systemic administration of human interferon-beta (IFN-beta) on experimental choroidal neovascularization which was caused by intensive laser photocoagulation at the posterior pole of monkey eyes. The regression of choroidal neovascularization was observed in IFN-treated monkeys. Histologically, retinal pigment epithelium (RPE) was remarkably abundant around choroidal neovascularization in the subretinal space, and the activity of neovascularization was weaker in IFN-treated monkeys than in untreated monkeys. These results indicate that IFN-beta promotes the proliferation of RPE and suppresses the activity of endothelial cells of neovascularization to cause regression of choroidal neovascularization. The results suggest that IFN-beta is clinically useful to treat the choroidal neovascularization of age-related macular degeneration.
We studied morphologically a long-term course of experimental choroidal neovascularization (ChNV) induced by krypton laser photocoagulation in the rat retina. Fifty-two weeks after photocoagulation, ChNV was enveloped completely by the retinal pigment epithelium. Vascular endothelial cells of ChNV were thin, with many fenestrations and wide lumen. The ChNV maintained the morphological characteristics of mature leaky capillaries similar to choriocapillaris. The lumen of the neovascularizations tended to be compressed by massive collagen fibers produced by the retinal pigmented epithelium. We found that experimental ChNV in the rat retina retains the characteristics of leaky capillaries for a long time unlike that in the monkey ChNV.
The ultrastructure of experimentally induced choroidal neovascularization was studied in correlation with dye leakage in indocyanine green (ICG) infrared fluorescence angiography. Newly formed vessels which demonstrated leakage of ICG extended into the subretinal space without enclosure of retinal pigment epithelium (RPE), and the endothelial cells were immature. Choroidal neovascularization which did not demonstrate leakage of ICG was enclosed by RPE without retinal detachment, and the endothelial cells were mature. The newly formed vessels with immature endothelium in the subretinal space that were covered with multiple layers of RPE demonstrated no leakage. These results show that ICG leaks form choroidal neovascularization which has immature vessels that are not enclosed by RPE and that extend into the subretinal space.
We studied the morphological effects of human interferon-beta on repair of the retinal pigment epithelium (RPE) after moderate dye laser photocoagulation in monkey eyes. In the control eyes, RPE cells were proliferating towards the center from the margin of the laser burn 3 days after photocoagulation. At day 14 after photocoagulation, a newly formed monolayer of RPE cells covered Burch's membrane to repair the lesion. In the eyes treated with interferon-beta by systemic administration, RPE cells had proliferated remarkably 3 days after photocoagulation. The RPE cells proliferated to form multiple layers on Burch's membrane even at day 14 after photocoagulation. These results suggest that interferon-beta promotes the proliferation to repair damaged RPE.
Experimentally produced choroidal neovascularization (ChNV) surrounded by a dark rim in indocyanine green (ICG) angiography was studied histopathologically. Dark rims were seen in 28% of ChNVs which were detected with ICG angiography 2 weeks after photocoagulation. During the developing stage of ChNV, the dark rim around it was seen in the early phase of ICG angiography, but in the late phase, the dark rim became unclear because of extravascular dye leakage. During the regressive stage, the dark rim was seen in all phases of angiography. It was especially clear in the late phase. Histopathologically, at the site of the dark rim the retinal pigment epithelial cells proliferated to surround the ChNV in the subretinal space during both stages. These results show that proliferated retinal pigment epithelium surrounding ChNV blocks the fluorescence of the choroid, and causes the dark rim. The dark rim is helpful for diagnosis of ChNV.
A series of 55 patients with ruptured cerebral aneurysms were treated with moderate removal of subarachnoid clot followed by intracranial irrigation with pH 8.0 Hartmann solution containing 1 mg/ml of methylpredonisolone sodium succinate after the aneurysmal clipping during early (before day 3) operation. Six (11%) of the 55 patients suffered vasospasm syndrome postoperatively. The clinical results are significantly better than a series of 68 patients operated on and treated before day 3 by intracranial irrigation with Hartmann solution (pH 8.0) only. The possible preventive effect of direct intracranial administration of steroid hormone is discussed.
We successfully produced, highly (78%) reproducible experimental choroidal neovascularization (ChNV) in the subretinal space of pigmented rats with intense diode laser photocoagulation. ChNV in the pigmented rat was characterized by rapid development of neovascular membrane and proliferation of retinal pigment epithelium in the subretinal space. This procedure may be useful as an experimental model for ChNV.
Pigmented rabbits were exposed for 2 hours to xenon light to evaluate the light induced retinal damage clinicopathologically. The xenon light was passed through a heat filter to avoid the influence of long waves, and through the fundus contact lens on the cornea to avoid focusing the light on the retina. No abnormal findings were detected in the retina in fluorescein angiography immediately after the light exposure. Three hours later, hyperfluorescence was found in the center of the exposed area and gradually grew worse. This was most marked twelve hours later. After 6 days, granular hyperfluorescence appeared at the edge of the damaged area and in 2 weeks the whole damaged area showed granular hyperfluorescence. Histopathologically, immediately after the light exposure, slight changes appeared in the retinal pigment epithelium (RPE). Twelve hours later, the cytoplasm of the RPE was edematous, and in 24 hours the RPE became necrotic, but the outer segments of the photoreceptor cells appeared intact. After 6 days, the RPE showed double layering, many macrophages were found in the subretinal space, and the outer segments of the photoreceptor cells were severely damaged. The RPE was primarily damaged and photoreceptor cells were damaged subsequently by xenon light without long waves.
We have reported previously that xenon light exposure without long waves primarily damages the retinal pigment epithelium (RPE) of pigmented rabbits. Alpha-tocopherol, which is a free radical scavenger, was administered systemically to pigmented rabbits before light exposure in order to evaluate the protective effect against retinal light damage. In fluoresceine angiography, at 12 hours after the light exposure, diffuse and marked hyperfluorescence was seen in the lower portion of the retina adjacent to the optic disc in the untreated group, and slight hyperfluorescence in a small area was seen in the treated group. Histopathologically, the RPE became necrotic 12 hours after the light exposure in the untreated group. In the treated group, only slight damage appeared in the RPE 12 hours after the light exposure. The light-induced retinal damage, particularly in the RPE, was remarkably reduced by administration of alpha-tocopherol before the light exposure.
Age-related macular degeneration is one of the major causes of severe visual loss is elderly individuals. However, relatively little is known about its etiology. The disease may be associated with senescence. Ultrastructural and immunohistochemical studies on SAM (senescence accelerated mouse) eyes were carried out to learn details of aging changes in the retinal pigment epithelium (RPE) and Bruch's membrane. SAM P 1 mice aged 2, 10, 14 months were examined in this study. The eyes were analysed for type IV collagen and heparan sulfate proteoglycan (HSPG) by the avidin-biotin-peroxidase complexes (ABC) method and post-embeddig immunolocalization with colloidal gold. With the ABC method, the basement membranes of both the RPE and the choriocapillaris showed markedly positive staining when treated with anti-type IV collagen antibody and moderately positive staining when treated with anti-HSPG antibody. In ultrastructural immunolocalization, both basement membranes showed fairly heavy labeling in response to the antibodies to type IV collagen, and moderate labeling in response to the antibodies to HSPG. With aging, the thickness of the basement membrane of the choriocapillaris and gold particle labeling by the antibodies to type IV collagen increased. The gold particle labeling by the antibodies to HSPG increased slightly, but was distributed sparsely. These results showed the advancing process of senescence changes in Bruch's membrane.
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A diode laser, emitting light in the near-infrared range (803 nm), was used for photocoagulation at mild, moderate, and strong intensities with or without intravenous administration of indocyanine green (ICG) in 7 eyes of 4 rhesus monkeys. The retinochoroidal lesions were studied histopathologically from 24 hours to 3 months after treatment, and choroidal vascular casts were studied by electron microscopy. Mild diode laser burns caused occlusion of the choriocapillaris and slight outer retinal damage. Moderate and severe burns caused more marked occlusion of the choriocapillaris, deep choroidal vessels, and choroidal nerves. There was little difference between ICG-enhanced and non-enhanced mild burns, but ICG-enhanced moderate and severe burns showed larger retinochoroidal lesions and more complete obstruction of the choriocapillaris than did burns without ICG enhancement. It seems that at moderate and strong levels, ICG-enhanced diode laser burns have more apparent effect on the retina and choroid, particularly on the choroidal vessels.
We demonstrated the distribution of sulfated proteoglycans in Bruch's membrane of Senescence Accelerated Mouse histochemically and ultrastructurally using cuprolinic blue in conjunction with specific enzyme treatments and nitrous acid digestion. Two kinds of proteoglycan filaments were observed in the inner and outer collagenous layers, i.e., small collagen fibril-associated filaments (11 nm in average length), and large filaments (32 nm in average length). Intermediate size filaments (25 nm in average length) were seen in the basement membranes of the retinal pigment epithelium and choriocapillaris. Chondroitinase AC treatment eliminated the staining of filaments in the collagenous layers (chondroitin sulfate). Chondroitinase ABC treatment also eliminated the staining of filaments in the collagenous layers (chondroitin sulfate and dermatan sulfate). Nitrous acid eliminated the staining of filaments in both basement membranes (heparan sulfate). Proteoglycans containing chondroitin sulfate and dermatan sulfate were associated uniquely with collagen fibrils. Heparan sulfate proteoglycans were associated with the basement membranes of the pigment epithelium and choriocapillaris. With aging, the thickness of the basement membrane of the choriocapillaris and the staining of the filaments in the basement membranes of the pigment epithelium and choriocapillaris (heparan sulfate proteoglycans) increased. Collagen fibers became disarranged and the staining of both filaments in the collagenous layers decreased. The results of the staining characteristics probably reflect the aging of Bruch's membrane.
BACKGROUND AND PURPOSE: Serial changes of anti-platelet-aggregating activity in the endothelial cells after experimental subarachnoid hemorrhage were studied in 30 feline two-hemorrhage models. METHODS: One hour or 2, 4, 7, or 14 days after mimic subarachnoid hemorrhage, ADP (40 mg/kg) was infused into the basilar artery via the right vertebral artery to activate circulating platelets. Immediately after ADP infusion, the basilar artery was fixed by intra-arterial perfusion with 1.5% glutaraldehyde in 0.1 mol/L phosphate buffer and was removed. The luminal surface was examined under a scanning electron microscope. RESULTS: One hour after subarachnoid hemorrhage, no platelets adhered or aggregated on the luminal surface. However, 4 to 7 days after subarachnoid hemorrhage, many platelets were observed adhering or aggregating on the luminal surface. CONCLUSIONS: These findings suggest the impairment of anti-platelet-aggregating activity of endothelial cells after subarachnoid hemorrhage. This impairment may be involved in inducing cerebral ischemia during cerebral vasospasm by causing platelet adhesion and aggregation.