Biomedical subjects

M Uyama

Publications and source records attributed to M Uyama.

At least 55 records · Page 3Linked to original sources

PubMed1997

Report on the nationwide epidemiological survey of exudative age-related macular degeneration in Japan.

The research Committee on Chorioretinal Degeneration, in cooperation with the Research Committee on the Epidemiology of Intractable Diseases, performed the second nationwide epidemiological survey of exudative age-related macular degeneration (AMD) in 1993. The number of exudative AMD patients in all ophthalmology departments throughout Japan was estimated to be 14,400 in 1993. This number was estimated to have almost doubled over the six year period since the initial survey in 1987. The number of people visiting ophthalmology departments due to exudative AMD was 53 males and 20 females per 100,000 population aged 50 years or over. The percentage of patients with bilateral disease increased with age and accounted for nearly 50% of those aged 80 years or over.

Age Distribution↗

PubMed1997

Expression of transforming growth factor-beta mRNA in experimental choroidal neovascularization.

PURPOSE: Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that modulates biological events as diverse as wound healing and angiogenesis and which may be important in the pathogenesis of choroidal neovascularization. We investigated the mRNA expression of TGF-beta isoforms in a model of experimental choroidal neovascularization induced by krypton-laser photocoagulation. METHODS: Rat TGF-beta 1, mouse TGF-beta 2 or TGF-beta 3 cDNAs was inserted into the pBluescript vector to prepare antisense and sense riboprobes. Intense laser burns were applied to the posterior poles of the eyes of pigmented rats according to a protocol described for producing choroidal neovascularization in these animals. At intervals up to 4 weeks after photocoagulation, the eyes were obtained and cut into thin sections. The sections were subjected to in situ hybridization with digoxigenin (DIG)-labeled single-strand riboprobes synthesized from each TGF-beta cDNA. RESULTS: In normal adult rat retinas and choroids, TGF-beta 1 mRNA was found only in cells of the ganglion cell layer, TGF-beta 2 mRNA was found in cells of the ganglion cell layer and choriocapillaris endothelium, whereas TGF-beta 3 mRNA was not detected at all. During the process of neovascularization, TGF-beta 1 and TGF-beta 2 mRNAs (the latter being expressed more prominently) were detected in retinal pigment epithelial cells, fibroblast-like cells and the endothelium of the neovascular region. TGF-beta 2 was the predominant isoform of TGF-beta, and its expression was especially strong in the endothelium of the choroidal neovascularization at 2 weeks. However, TGF-beta mRNAs was decreased in cells 4 weeks after photocoagulation. CONCLUSIONS: Our findings suggest that TGF-beta may act in the retina as a neurotrophic agent, since TGF-beta 1 is normally transcribed in ganglion cells and TGF-beta 2 is also transcribed in ganglion cells and choriocapillaris endothelium. TGF-beta 1 and TGF-beta 2 mRNA expression were increased in photocoagulated lesions from 3 days to 2 weeks after laser treatment. Therefore, it is likely that TGF-beta acts as a mediator of the neovascularization process.

Animals↗

PubMed1997

Morphologic characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL mice.

Morphologic characteristics of retinal degeneration induced by a single systemic administration of N-methyl-N-nitrosourea (MNU) in mice was investigated. The aim was to characterize the MNU-induced retinal lesions in mice and compare them with human retinitis pigmentosa. A dose of 60 mg/kg body weight MNU, injected intraperitoneally into male and female C57BL mice, evoked progressive retinal degeneration in all treated mice, while control mice remained normal. An early change was photoreceptor apoptosis followed by infiltration of macrophages and swelling of the pigment epithelial cells with phagosomal inclusions for apoptotic photoreceptor cell removal. Loss of the majority of photoreceptor cells occurred within a week. Then, Feulgen-positive corpuscles, indicative of an aggregation of degenerative photoreceptor elements, vitread the outer limiting membrane were surrounded by Müller cell processes, and the duplication of the pigment epithelial cells sclerad the outer limiting membrane were seen 2 and 3 weeks after the treatment. Finally, the Feulgen-positive corpuscles disappeared and Müller cell processes were in direct contact with the continuous lining of the single layer of pigment epithelial cells. As in retinitis pigmentosa in humans, the primary event was loss of photoreceptor cells by apoptosis, but the migration of the pigment epithelial cells within the retina was not seen in the present model.

Animals↗

PubMed1997

Smoking and neovascular form of age related macular degeneration in late middle aged males: findings from a case-control study in Japan. Research Committee on Chorioretinal Degenerations.

AIMS: The risk of smoking habits for developing the neovascular form of age related macular degeneration (neovascular form of AMD) were studied by a case-control study in Japan. METHODS: 56 male patients with the neovascular form of AMD and 82 healthy male controls, aged 50 to 69 years, were enrolled. A self administered questionnaire provided necessary information for the study subjects. Questions on smoking included whether the study subjects have ever smoked or not, and if smoked, depth of smoke inhalation, use of extra filter, age at starting smoking, average number of cigarettes smoked per day, and duration of smoking. When a smoker had stopped smoking, age at cessation was also recorded. Unconditional logistic analysis was adapted to calculate age adjusted odds ratios and their 95% confidence intervals (CIs) for smoking related factors. RESULTS: Age adjusted odds ratio of developing the neovascular form of AMD was 2.97 (95% CI 1.00-8.84) for current smokers and 2.09 (0.71-6.13) for ex smokers, compared with non-smokers. All smoking habit/smoking history related variables such as use of extra filter, smoke inhalation level, age at starting smoking, duration of smoking, and Brinkman index were found to be significantly related to an increased risk of the neovascular form of AMD. CONCLUSIONS: Suggested is the strong possibility that cigarette smoking enhances the neovascular form of AMD risk in late middle aged males, though the magnitude of risk by smoking variables might be overestimated, in part, because of health oriented controls.

Aged↗

PubMed1997

[Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance. Report 1].

We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed all of the posterior temporal ciliary arteries, to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed using scanning laser ophthalmoscope immediately, and 2 days after occlusion. These findings were compared with histopathological findings from the same specimen. Immediately after occlusion, choroidal vessels were filled with the red blood cells in the lesion that showed hypofluorescence in both types of angiography. Two days after occlusion, the fundus had a grayish white edematous appearance which was similar to choroidal infarction. The retinal pigment epithelial cells. (RPEs) in infarcted lesion progressed to liquefied necrosis. Fluorescein angiography showed hyperfluorescence in the lesion, and ICG angiography showed hypofluorescence in the early phase, but hyperfluorescence at the margin of the lesion in the late phase. This result showed that damaged RPEs were stained by ICG dye. In reading ICG angiography, we have to consider that the ICG angiogram is greatly modified by the condition of the RPEs.

Animals↗

PubMed1997

['Ischemic tolerance' in ischemia-reperfusion injury in the optic nerve in rats].

Brief ischemia caused by high intraocular pressure induced tolerance to subsequent ischemia-reperfusion injury in rats. Male Wistar rats were subjected to 15 minutes of ischemia. This ischemic injury did not show distinct axonal damage in the optic nerve in electron microscopy. 1, 2, 4, 7, and 14 days after the first 15 min ischemia, the rats were subjected to a second ischemia for 45 minutes (ischemic tolerance). After 1 week, the rats were perfusion fixed and the optic nerves were processed for light and electron microscopy. Samples of the axonal density in the central optic nerve 2 mm behind the lamina cribrosa were observed and counted an electron micrographs. In axonal morpometric findings, 2 days and more after brief ischemia, the damage was lessened more than after 45 minutes ischemia (control) and the difference was significant. This 'ischemic tolerance' induced by brief ischemia might be considered the same stress as brain ischemia-reperfusion injury.

Animals↗

PubMed1997

[Ornithine induced retinopathy in the rat--1. Histopathological study on the retinal pigment epithelium].

An intravitreal injection of a small amount of 1-ornithine hydrochloride damages the retinal pigment epithelium (RPE) selectively in monkey eyes. In this paper, we examined the rat eye and observed similar results. Clinically, retinal edema appeared immediately after injection and showed hyperfluorescence on a fluorescein angiograph after 3 days. Histopathologically, RPE showed marked swelling 3 hours after injection, then became necrotic and disappeared gradually. One month after injection, retinal structure was maintained in the area where RPE regenerated to cover Bruch's membrane, but in the area where RPE cells disappeared, the photoreceptor cells and choriocapillaris degenerated and finally disappeared. In the eyes injected intravitreally with NaCl solution of equivalent osmosis microvacuoles were seen but no necrotic change in RPE. Thus, a small amount of ornithine damaged RPE selectively, and induced disappearance of the photoreceptors and choriocapillaris secondarily.

Animals↗

PubMed1997

[Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance. Report 2].

We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed the posterior ciliary arteries to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed at one week, and one month after occlusion. These findings were compared with histopathological findings. One week after occlusion, the area of choroidal infarct showed occlusion of choriocapillaris and proliferation of the retinal pigment epithelial (RPE) cells, this area showed hypofluorescence in the early phase ICG angiography. The hypofluorescence area increased in the late phase. One month after occlusion, the lesion showed loss of choriocapillaris at the center and proliferation of fibroblast-like cells at the edge of the lesion. The subretinal strand showed hyperfluorescence in late phase ICG angiography. Proliferated RPE cells masked ICG fluorescence in the late phase. Fibroblast-like cells showed tissue staining. When reading ICG angiography, we have to take into account that the ICG angiogram is greatly modified by condition of the RPE.

Animals↗

PubMed1997

[Ornithine induced retinopathy in rat--2. Process of disappearance of choriocapillaris].

We observed the process of disappearance of the choriocapillaris after loss of the retinal pigment epithelium (RPE) induced by intravitreal injection or ornithine. Three hours after administration of ornithine, the RPE cells swelled remarkably in the posterior pole, but, the endothelial cells of the choriocapillaris remained intact. At 3 days, the RPE cells became necrotic, but the choriocapillaris still preserved its in normal appearance. At 7 days, RPE disappeared completely in the posterior pole and the choriocapillaris displayed evidence of atrophy; the swollen lumen of the choriocapillaris became narrow the cytoplasm of the endothelium was swollen, and the number of fenestrae was reduced. On the other hand, these changes were not seen where the RPE remained. At 14 days, in the posterior pole, the lumen of the choriocapillaris occluded by the swollen endothelial cells. At 28 days, the choriocapillaris completely disappeared and the large choroidal vessel was directly in contact with Bruch's membrane. These results showed that the RPE is correlated with the presence of the choriocapillaris.

Animals↗

PubMed1997

[Expression of basic fibroblast growth factor and fibroblast growth factor receptor 1 in the experimental retinal vein occlusion model].

Retinal ischemia promotes retinal neovascularization. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are important growth factors for neovascularization. We did experimental retinal vein occlusion (RVO) and examined the expression of basic FGF and FGF receptor 1(one of the basic FGF receptors) by in situ hybridization. We used adult pigmented rats (Brown-Norway strain). Dye laser photocoagulation (577 nm) was applied to the retinal arteries and veins within two disc diameters of the optic nerve head to injure the retinal vessels. After one week, laser photocoagulation was applied to only the retinal veins to occlude them (RVO model). As a control, laser photocoagulation was applied to the posterior retina avoiding the retinal vessels. After treatment, the eyes were removed and 10 microns thick cryostat-cut chorioretinal section were used for in situ hybridization with probes as mentioned above. In the RVO model, expression of messenger RNA of basic FGF (b-FGF) and FGF receptor 1 increased in the inner nuclear layer and the inner segment of the photoreceptors, and appeared in the retinal vessel wall in the early stage. This shows that b-FGF and FGF receptor 1 increased in the ischemic retina, and were produced on the retinal vessel wall. This suggests that b-FGF may be involved in protection, regeneration, and proliferation of the retinal vascular endothelial cells in retinal circulatory disturbance.

Animals↗

PubMed1997

[Results of vitreous surgery for proliferative vitreoretinopathy].

During the past four years, we performed vitreous surgery on 73 eyes with rhegmatogenous retinal detachments complicated with severe proliferative vitreoretinopathy (PVR). We analyzed the surgical outcome of PVR according to the revised classification of PVR Grade C (1991). After a mean follow-up period of 19 months, the retinas were successfully reattached in 62 of 73 eyes (85%). The reattachment rate in the eyes with only posterior proliferation was high (96%), regardless of the extent of posterior proliferation. However, the reattachment rate in the eyes associated with anterior proliferation was markedly low (57%), depending on the extent of anterior proliferation. Among 62 eyes with successfully reattached retinas, 39 eyes (63%) had an improved postoperative visual acuity. These results demonstrated that the eyes with anterior PVR have a worse reattachment rate than the eyes with only posterior PVR. Using the revised classification of PVR, we were able to analyze the surgical outcome of PVR which could not be classified by the old classification.

Adolescent↗

PubMed1996

In situ hybridization analysis of substance P receptor in the rat retina.

Substance P receptor is known to provide a principal interface between tachykinin peptides and tachykinin-sensitive cells in retinal circuitry and to produce several physiological functions such as excitation of ganglion cells. We reported results of in situ hybridization analysis of substance P receptor in rat retina using digoxigenin-labeled RNA probes to yield discrete cell labeling. Distinct hybridization signal was present in a great majority of ganglion cells that provide retinal fibers to a central target. It was also present in a subpopulation of amacrine cells. Following optic nerve crush, ganglion cells lost their hybridization signal in a time-dependent manner, while hybridization-positive amacrine cells were persistently seen. From the results, we identified the hybridization message as distinctly localized to two systems, output cells and intrinsic cells in retinal circuitry.

Animals↗

PubMed1996

Immunolocalization of basic fibroblast growth factor during wound repair in rat retina after laser photocoagulation.

BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key role in wound repair. We studied the immunohistochemical localization of bFGF during wound repair in the rat retina after laser photocoagulation. METHODS: Krypton laser photocoagulation was performed on the eyes of pigmented rats. The eyes were enucleated on days 1, 3, 7, 14 and 28 after the photocoagulation, and the immunohistochemical localization of bFGF was assessed. Two different monoclonal antibodies and one polyclonal antibody against bFGF as first antibodies were used. RESULTS: Marked immunoreactivity for bFGF was found in the ganglion cell layer, and weak immunoreactivity for bFGF was found in the retinal pigment epithelial (RPE) cells of the normal adult rat retina. On day 3 after laser photocoagulation, the nuclei and cytoplasm of proliferating RPE cells at the center of the photocoagulated lesion showed intense bFGF immunoreactivity. The nuclei of RPE cells around the lesion showed intense bFGF immunoreactivity. Macrophages that migrated into the lesion showed positive staining for bFGF. These immunoreactivity decreased with time. Controls (0.05 M Tris-HCl buffer, normal serum, or these same antibodies preabsorbed with bFGF) did not show positive staining. CONCLUSION: The finding of an elevated expression of bFGF immunoreactivity in the photocoagulated lesion suggests that bFGF may play a role in wound repair in the rat retina after laser photocoagulation.

Animals↗

PubMed1996

High intraocular pressure-induced ischemia and reperfusion injury in the optic nerve and retina in rats.

PURPOSE: The purpose of this paper is to describe the damage caused to the retina and the axons of the optic nerve by acute ischemia-reperfusion injury and the extent to which optic nerve damage correlates with the duration if ischemia due to high intraocular pressure (IOP). METHODS: Acute ischemia in the retina and optic disc was induced in albino rats by increasing the IOP to 110 mmHg for a period of 45-120 min. Thereafter, the eyes were reperfused at normal IOP after 7 days. The retina and optic nerve were examined by light and electron microscopy, and morphometrical counts of the optic nerve axons were performed. RESULTS: After 45 min of ischemia, electron microscopic examination revealed swelling of mitochondria and degeneration of neurotubules on axons in cross sections of the optic nerve. The axonal counts in eyes subjected to 45 min of ischemia were 29% lower than in control eyes. After 60 min of ischemia, there were distinct disruptions of mitochondria and degeneration of the axons. After 90 min of ischemia, numerous axons showed degeneration with disordered myelin sheaths. Neuronal cell death was seen in the retina, mainly in the ganglion cell layer. CONCLUSION: Damage to the retinal ganglion cell layer and the optic nerve was evident after only 45 min of ischemia in normal eyes. This experiment suggests that seriously injured eyes must be protected from high IOP; if IOP elevation is required during vitrectomy, it is essential to reduce the duration of interruption of blood flow to a minimum.

Animals↗

PubMed1996

Expression of basic fibroblast growth factor mRNA in developing choroidal neovascularization.

PURPOSE: Basic fibroblast growth factor (bFGF) is an angiogenic peptide that may be important in the pathogenesis of choroidal neovascularization. We attempted to determine the transcription of the bFGF gene during the development of experimentally induced choroidal neovascularization. METHODS: Rat bFGF cDNA was inserted in the pBluescript to prepare antisense and sense riboprobes. Multiple krypton laser burns were applied to the posterior poles of the eyes of pigmented rats according to a protocol described for producing subretinal neovascularization in these animals. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into thin sections. The sections were subjected to histopathological analysis, cell proliferation study, or in situ hybridization with digoxigenin (DIG)-labeled single-strand riboprobes synthesized from rat bFGF cDNA. RESULTS: In normal adult rat retinas, bFGF mRNA expression was mainly observed in the ganglion cell layer and the inner nuclear layer. After laser photocoagulation, proliferation of RPE cells, fibroblast-like cells and cells in the choroid in the lesions were observed. Expression of bFGF mRNA was observed in the lesions 3 days to 2 weeks after laser treatment. Signals of bFGF mRNA were detected in the proliferating RPE-like cells, choroidal vascular endothelial cells and fibroblast-like cells, all of which are essential for neovascularization. However, bFGF mRNA expression was no longer detectable in these cells 4 weeks after photocoagulation. CONCLUSIONS: Our findings indicate that bFGF is normally transcribed in ganglion cells and the inner nuclear cell layer. During the neovascularization that followed laser photocoagulation, bFGF mRNA expression was detected within the laser lesions. It is thus probable that bFGF acts as a mediator in the neovascularization process.

Animals↗

PubMed1996

Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina.

Retinal degeneration was induced by a single intraperitoneal injection of N-methyl-N-nitrosourea in female Sprague-Dawley albino rats at 50 days of age by two dose regimens, which were observed sequentially at 24, 48, and 72 hours and 7, 21, and 35 days after the treatment. After a dose of 75 mg/kg, methylnitrosourea evoked progressive retinal degeneration in all treated rats whereas a dose of 50 mg/kg was less effective. The 75-mg/kg-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism, as confirmed morphologically and by the terminal dUTP nick end labeling method. Apoptosis had already started at 24 hours after the treatment and was completed by day 7. During the photoreceptor degeneration, proliferation of glial fibrillary acidic protein and vimentin-positive Müller cells as detected by proliferating cell nuclear antigen labeling appeared at 48 hours and was prominent 72 hours after the treatment, and macrophage infiltration within the retina as recognized by ED1 positivity was maximal 7 and 21 days after the treatment. Retinal degeneration was also induced in female Brown-Norway colored rats in a similar dose-dependent manner. Pigment epithelium was discontinuous above Bruch's membrane, and migration of the swollen pigment epithelium toward the inner nuclear layer was seen 7 days after the treatment. Therefore, as also confirmed electron microscopically, the most striking change was the destruction of photoreceptor cells by the apoptotic process, followed by Müller cell proliferation, pigment epithelium migration, and macrophage infiltration for cell debris phagocytosis, resulting in a thin remnant of retina with attenuated inner nuclear cells in direct contact with Bruch's membrane or with the pigment epithelium and/or with the Müller cells 35 days after the treatment.

Animals↗

PubMed1996

[Expression of basic fibroblast growth factor and its receptor in the process of wound healing of rat retina after laser photocoagulation].

We investigated the expression of mRNA of basic fibroblast growth factor (bFGF) and FGF receptor 1 in rat retina after laser photocoagulation using in situ hybridization method. Pigmented rats (Brown Norway strain) received weak photocoagulation by krypton laser (500 microns, 0.05 sec, 60 mW) in the posterior retina. On 1, 3, 5, 7, 14 days after laser photocoagulation, the rats were fixed by perfusion with phosphate-buffered 4% paraformaldehyde and the eyes were enucleated. The eyes were further fixed by immersion in the same fixative, then quickly frozen in liquid nitrogen and finally sectioned with a cryostat. In situ hybridization was performed on frozen sections with digoxigenin (DIG) labeled riboprobes synthesized from rat bFGF cDNA and FGF receptor 1 cDNA. In normal chorioretinal tissue, the signals of bFGF and FGF receptor 1 mRNA were seen in the ganglion cell layer and inner nuclear layer. On day 3 after photocoagulation, we observed expression of bFGF and FGF receptor 1 mRNA in the proliferating retinal pigment epithelial (RPE) cells and endothelial cells of choriocapillaris at the photocoagulated lesion. We also observed expression of bFGF mRNA in some macrophage-like cells. On day 14 after photocoagulation, these expressions had disappeared. Our results suggest that bFGF may be involved in the process of retinal wound healing after laser photocoagulation.

Animals↗

PubMed1996

Immunohistochemical proof of origin of macrophages in laser photocoagulation lesion in the retina.

The origin of the macrophages which appear in the subretinal space after laser photocoagulation on the rat retina was investigated using immunohistochemistry. The majority of macrophages located in laser lesions were found to be positive to staining for the specific rat monocyte/macrophage marker (ED1). The number of macrophages and activated macrophages were abundant after intense laser photocoagulation in which choroidal neovascularization was induced. After the retinal pigment epithelium (RPE) was damaged by intravenous administration of sodium iodate, the number of migrating macrophages in the subretinal space of lasered areas significantly decreased to a level comparable to the level found in control animals. These results suggested that the macrophages were derived mainly from monocytes in the blood, not from RPE cells, and that they may play a role in the development of the choroidal neovascularization.

Animals↗