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S Amano

Publications and source records attributed to S Amano.

At least 37 records · Page 2Linked to original sources
PubMed2003

Angiotensin II stimulates platelet-derived growth factor-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation.

Platelet-derived growth factor-BB (PDGF-BB) is a potent mitogen and chemoattractant for microvascular endothelial cells and glial cells in the retina and is thus involved in the development of proliferative diabetic retinopathy. However, relatively little is known about the regulation of PDGF-B gene expression in retinal cells. In this study, we cloned partial complementary DNAs (cDNAs) encoding bovine PDGF-B and examined the effects of angiotensin II (Ang II), which is also implicated in the pathogenesis of diabetic retinopathy, on PDGF-B gene expression in bovine cultured retinal pericytes. Ang II was found to up-regulate PDGF-B messenger RNA (mRNA) levels in bovine retinal pericytes. Telmisartan, a newly developed Ang II type 1 receptor antagonist, or an antioxidant N-acetylcysteine significantly inhibited PDGF-B gene induction in Ang II-exposed pericytes. The present results suggest that Ang II-type 1 receptor interaction could stimulate PDGF-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation and could thus be involved in the progression of diabetic retinopathy.

Acetylcysteine↗
PubMed2002

Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction.

Reducing sugars can react nonenzymatically with the amino groups of proteins to form Amadori products and subsequently cross-linked, heterogeneous fluorescent derivatives called advanced glycation end products (AGE). AGE can arise in vivo from various types of reducing sugars or dicarbonyl compounds and their formation and accumulation are known to progress during normal aging. In individuals with diabetes mellitus, this progression is greatly accelerated. The aim of the present study was to investigate which kinds of serum AGE components were associated with the severity of diabetic retinopathy in 72 type 2 diabetic patients without renal dysfunction. Serum levels of glucose-, glyceraldehyde- or methylglyoxal-derived AGE (methyl-AGE) were measured by an enzyme-linked immunosorbent assay. No significant correlations were found between serum levels of various AGE and HbA1c level, current age, systolic and diastolic pressure, diabetes duration, serum creatinine or blood urea nitrogen level in type 2 diabetic patients. A significant elevation of serum glucose-AGE was found to be associated with severity of diabetic retinopathy. While no differences in serum methyl-AGE levels were found between patients with diabetic retinopathy and those without, serum levels of glyceraldehyde-AGE showed a tendency to increase as normal retinal status advanced to simple and proliferative retinopathy (p = 0.06). The present results suggest that among various types of AGE, glucose-AGE serum levels may be a useful marker of diabetic retinopathy in type 2 diabetic patients without renal dysfunction.

Diabetes Mellitus, Type 2↗
PubMed2002

Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats.

Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the mechanisms for the development and progression of diabetic nephropathy are not fully understood, platelet activation may participate in its pathogenesis by promoting microthrombus formation. In this study, we investigated the effects of dilazep hydrochloride, an antiplatelet agent, on the development and progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a type 2 diabetes mellitus animal model. Administration of dilazep hydrochloride significantly reduced the increase of urinary protein excretions and N-acetyl-beta-D-glucosaminidase (NAG) activity in OLETF rats. Furthermore, dilazep hydrochloride treatment prevented glomerulosclerosis and tubular atrophy and reduced positive staining for type IV collagen in the glomeruli of diabetic rats. These results indicate that platelet activation plays a dominant role in the development and progression of diabetic nephropathy. Our study suggests that dilazep hydrochloride is a valuable new drug for the treatment of diabetic patients with nephropathy.

Acetylglucosaminidase↗
PubMed2002

Up-regulation of vascular endothelial growth factor and down-regulation of pigment epithelium-derived factor messenger ribonucleic acid levels in leptin-exposed cultured retinal pericytes.

Leptin, a circulating hormone secreted mainly from adipose tissues, is involved in the control of body weight. Recently, leptin was found to be an angiogenic factor and its vitreous levels were shown to be elevated in patients with angiogenic eye diseases such as proliferative diabetic retinopathy. However, the role of leptin in diabetic retinopathy is not fully understood. Since pericyte loss and dysfunction have been considered to be one of the characteristic changes of the early phases of diabetic retinopathy, we investigated the effects of leptin on the growth and function of bovine cultured retinal pericytes. Although it did not affect cell growth, leptin significantly up-regulated pericyte messenger ribonucleic acid levels of an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF). Leptin was also found to significantly inhibit gene expression of pigment epithelium-derived factor (PEDF), the most potent angiogenesis inhibitor in the mammalian eye, in pericytes. The present study suggests that leptin might elicit angiogenesis through VEGF induction as well as PEDF suppression in pericytes and could thus be involved in the development and progression of diabetic retinopathy, especially in obese insulin-resistant patients.

Animals↗
PubMed2002

Pigment epithelium-derived factor Met72Thr polymorphism in patients with diabetic microangiopathy.

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye. We, along with others, have very recently found that loss of PEDF is involved in the development and progression of diabetic retinopathy. However, there are no studies on the allelic effects of PEDF gene polymorphism in diabetic retinopathy. In this study, we investigated whether a functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) of the PEDF gene, is associated with microangiopathy in 143 patients with diabetes. We found that there were no significant associations between PEDF Met72Thr gene polymorphism and diabetic microangiopathy. These observations suggest that these genetic variants might not be involved in the mechanism of diabetic microangiopathy in patients with diabetes.

Adult↗
PubMed2001

Importance of balance between extracellular matrix synthesis and degradation in basement membrane formation.

The epidermal basement membrane (BM) plays important roles in adhesion between epidermis and dermis and in controlling epidermal differentiation. In a skin-equivalent (SE), components of the epidermal BM such as laminin 5 and type IV and VII collagens were detected in conditioned media and in basal keratinocytes. Despite production of these BM components, however, BM was rarely observed at the dermal-epidermal junction. One possible explanation for the absence of BM in SEs is that matrix metalloproteinases (MMPs) degrade newly synthesized extracellular matrices. In fact, several MMPs, such as MMPs-1, 2, 3, and 9, were observed to be present in conditioned media and some of them were in active forms. Tissue inhibitor of metalloproteinase (TIMP)-2 was not detected, although TIMP-1 was present. BM degradation activity presumably exceeds BM formation activity in the SE, resulting in the absence of lamina densa at the dermal-epidermal junction. Synthetic MMP inhibitors CGS27023A and MMP inhibitor I, which inhibit MMPs 1, 2, 3, and 9, markedly augmented deposition of laminin 5 and type IV and VII collagens at the dermal-epidermal junction, resulting in formation of continuous epidermal BM. These results suggest that the balance between synthesis and degradation of BM components is important for BM formation.

Animals↗
PubMed2001

Neuronal microdysgenesis and acquired lesions of the hippocampal formation connected with seizure activities in Ihara epileptic rat.

The present study was designed to examine the morphological features of the hippocampal formation in the Ihara epileptic rat (IER), and to characterize genetically programmed lesions and acquired lesions connected with seizure activities. Neuropathological investigation of the hippocampal formation was performed in four separate groups, 2-month-old IERs with neither abnormal behaviors nor any seizure activity, and 12-month-old IERs of both sexes with abnormal behaviors, circling seizures or generalized tonic-clonic convulsions. In every IER examined, there were invariable and fundamental neuropathological findings consisting of abnormal neuronal clusters in the CA1 of the hippocampal formation. Moreover, disarrangement of neuronal cells, such as dispersion and gaps in lamination of pyramidal neurons, were observed. These changes were thought to represent genetically programmed lesions, neuronal microdysgenesis, because they were common findings in 2-month-old and 12-month-old IERs of both sexes. An enlargement of the dentate gyrus was also found in rats that experienced generalized tonic-clonic convulsions or circling seizures. This enlargement of the dentate gyrus, on the other hand, was categorized as a secondary and acquired lesion connected with seizure activities. It is suggested that the neuronal microdysgenesis in the hippocampal formation of IER has an intimate relationship with epileptogenesis and/or an enhancement of seizure susceptibility.

Animals↗
PubMed2001

Expression of brain specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the developing and adult hippocampus of Ihara's epileptic rats.

Ihara's epileptic rats (IER) is an animal model of temporal lobe epilepsy with mycrodysgenesis, that exhibit abnormal migration of hippocampal neurons and recurrent spontaneous seizures. As an attempt to elucidate the roles of extracellular matrix molecules in the epileptogenecity and mossy fiber sprouting, immunohistochemical localization of brain specific chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, was examined in the hippocampus of postnatal IER and Sprague-Dawley (SD) rats using monoclonal antibodies 1G2 against neurocan and 6B4 against phosphacan. There was no difference in the expression of these two CSPGs between IER and SD rats in the 1st postnatal week. However, the expression of neurocan was poor in the hippocampus of IER in the 2nd and 3rd weeks whereas intense labeling of neurocan was present throughout the hippocampus of SD rats. Labeling of neurocan was almost absent in the hippocampus, while phosphacan was diffusely expressed in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus at the 2nd month after birth. There was no difference in the expression of neurocan and phosphacan between IER and SD rats at the 2nd month after birth. By contrast, phosphacan was reduced in the inner molecular layer of the dentate gyrus in 8-month-old IER, while neurocan was reexpressed in the outer molecular layer and hilus in 3- and 8-month-old IER. It was suggested that the insufficient expression of neurocan may affect the development of neuronal organization in the hippocampus, and that the remodeling of extracellular matrix in the dentate gyrus may contribute to the mossy fiber sprouting into the inner molecular layer.

Aging↗
PubMed2001

Contribution of neurons to habituation to mechanical stimulation in Caenorhabditis elegans.

In Caenorhabditis elegans, a light touch induces a locomotor response. Repeated touches, however, result in an attenuation of response, that is, habituation. Withdrawal responses elicited by anterior touch are controlled by anterior mechanosensory neurons (AVM and ALMs), and by four pairs of interneurons (AVA, AVB, AVD, and PVC) (Chalfie et al., 1985; White et al., 1986). To identify the neurons that participate in habituation, we ablated these neurons with a laser microbeam and investigated the resulting habituation of the operated animals. The animals lacking both left and right homologues AVDLR were habituated more rapidly than intact animals. We propose that chemical synapses at AVD play a critical role in the habituation of intact animals.

Animals↗
PubMed2001

Expression of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in corneal lymphangiogenesis.

Lymphangiogenesis has been reported in vascularized corneas. However, the molecular mechanisms of lymphangiogenesis in the cornea are still unclear. Since lymphatic vessels may contribute to a decreased success rate of keratoplasty in vascularized cornea by accelerating antigen recognition and graft rejection, elucidation of the mechanisms of corneal lymphangiogenesis will facilitate the inhibition of lymphatic vessels and may improve the outcome of keratoplasty. This study aimed to examine the expression of vascular endothelial growth factor-C (VEGF-C), which is the only endogenous lymphangiogenic factor reported so far, and one of its receptors, vascular endothelial growth factor receptor-3 (VEGFR-3), in corneal lymphangiogenesis. A rat model was used in which silver nitrate application resulted in corneal circumferential neovascularization. The presence of lymphatic vessels in the rat injured cornea was examined with electron microscope. Corneal VEGF-C and VEGFR-3 mRNA levels were quantified with competitive reverse transcription polymerase chain reaction (RT-PCR), and VEGF-C and VEGFR-3 proteins were studied in situ using immunohistochemical analysis. Electron microscopy revealed lymphatic vessels in the vascularized rat corneas. Competitive RT-PCR demonstrated that the expression of VEGF-C mRNA in the rat cornea was normally absent, and was dramatically up-regulated 3 days after the injury, which gradually decreased. The VEGFR-3 expression in the rat cornea was minimally detected before the injury and was up-regulated 3 and 7 days after the injury. It was also minimally detected 2 and 4 weeks after the injury. In immunohistochemical analysis of the rat cornea 3 days after the injury, VEGF-C was mainly detected in inflammatory cells, and VEGFR-3 was demonstrated in several new vessels in the corneal stroma. These data suggest that VEGF-C and VEGFR-3 are pathophysiologically relevant endogenous factors in corneal lymphangiogenesis.

Animals↗
PubMed2001

Genetic analysis of cataract in Ihara epileptic rat.

We analyzed the mode of inheritance of cataract in the Ihara epileptic rat (IER) by crossing experiments, and mapped cataract-related genes by linkage analysis. Cataract did not develop in the F1 animals, but it developed in both male and female animals of backcross and F2. The occurrence rate of cataract was 48.5% in the backcross progeny and 19.4% in the F2 progeny. Thus, the character was considered to be inherited by the autosomal recessive mode. We found two groups that differed according to the time of onset among the backcross and F2 progeny: an early-onset group (EOG), in which cataracts developed by about 4 months after birth, and a late-onset group (LOG), in which cataracts developed 8 months or more after birth. Linkage analysis indicated the presence of one cataract gene each on Chromosome (Chr) 8 and Chr 15, and the cataract was demonstrated to be governed by more than one gene. The gene on Chr 8 was named Catil, and that on Chr 15. Cati2. Catil was involved in the occurrence of cataract, and the conditions required for cataract to develop were Cati1i/Cati1i or Cati1i/Cati1w. However, in the cataract rats with Cati1i/ Cati1w, the allele of Cati2 was always Cati2i/Cati2i. Cati2 was involved in the timing of onset of the cataract, and the precondition for early onset was Cati2i/Cati2i.

Age of Onset↗
PubMed2001

Anterior capsular contraction after cataract surgery in vitrectomized eyes.

PURPOSE: To assess the contraction of continuous curvilinear capsulorhexis after cataract surgery in eyes with past pars plana vitrectomy. METHODS: In a prospective study, 16 eyes of 16 patients underwent phacoemulsification and implantation of a foldable acrylic intraocular lens after pars plana vitrectomy. Eyes after intensive or repeated vitrectomy were not included. Twenty eyes of 19 patients served as age-matched controls. Aqueous flare intensity was measured using the laser flare-cell meter 1 year after surgery. The area of anterior capsular opening (ACO) was determined by diaphanoscopy using the anterior eye segment analysis system EAS-1000 at 1 day and 1 year postoperatively. RESULTS: There was no significant difference in the mean ACO area between the vitrectomy and control groups both at 1 day and 1 year postoperatively. Aqueous flare intensity 1 year after surgery was slightly higher in the vitrectomy group, but the difference was not statistically significant. CONCLUSION: Eyes after simple vitrectomy are not at a higher risk of ACO contraction following cataract surgery.

Aged↗
PubMed2001

Factors affecting the forward shift of posterior corneal surface after laser in situ keratomileusis.

PURPOSE: To evaluate the anteroposterior movement of the corneal back surface after laser in situ keratomileusis (LASIK). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred ninety-six eyes of 120 subjects with myopic refractive errors of -2.0 to -12.5 diopters. INTERVENTION: LASIK was performed. Corneal topography of the posterior corneal surface was obtained with the scanning slit topography system before and 1 month after surgery. MAIN OUTCOME MEASURES: The amount of forward shift of the posterior corneal surface was determined. Multiple regression analysis was used to assess the factors that affect the forward shift of the posterior corneal surface. RESULTS: After surgery, the posterior corneal surface displayed mean forward shift of 40.9 +/- 24.8 micrometer. Explanatory variables relevant to the forward shift of corneal posterior surface were, in the order of magnitude of influence, the amount of laser ablation (partial regression coefficient B = 0.561, P < 0.0001), preoperative corneal thickness (B = -0.176, P = 0.00096), and preoperative intraocular pressure (B = 1.676, P = 0.0053). Preoperative refraction and achieved myopic correction showed collinearity with the amount of laser ablation. CONCLUSIONS: LASIK induces a forward shift of the cornea. Eyes with thinner corneas, higher intraocular pressure, and higher myopia requiring greater laser ablation are more predisposed to the anterior shift of the cornea.

Adult↗
PubMed2001

Corneal irregular astigmatism and contrast sensitivity after photorefractive keratectomy.

OBJECTIVE: To investigate the relation between contrast sensitivity and corneal irregular astigmatism in eyes after photorefractive keratectomy (PRK). DESIGN: Prospective observational case series. PARTICIPANTS AND CONTROLS: Seventy-nine eyes without corneal haze 6 months or more after PRK and 30 normal control eyes. METHODS: Videokeratography was taken with TMS-1 (Computed Anatomy Inc. New York, NY), and contrast sensitivity for day and night vision was measured using a Multivision Contrast Tester 8000 (Vistech Consultants, Inc., Dayton, OH). MAIN OUTCOME MEASURES: Regular and irregular astigmatism (asymmetry and higher order irregularity components) were computed using Fourier series harmonic analysis of the videokeratography data. Area under the log contrast sensitivity function (AULCSF) was calculated from the contrast sensitivity data taken at five spatial frequencies. RESULTS: After PRK, AULCSFs were significantly smaller for day vision (P = 0.007, unpaired t test) and night vision (P = 0.020) compared with normal controls. AULCSFs for day vision were significantly negatively correlated with asymmetry (Pearson's correlation coefficient, R = -0.23, P = 0.049) and higher order irregularity (R = -0.33, P = 0.004) components but not with the regular astigmatism component (P > 0.3). AULCSF for night vision correlated significantly with asymmetry (R = -0.31, P = 0.013) and higher order irregularity (R = -0.30, P = 0.016) components but not with the regular astigmatism component (P > 0.3). CONCLUSIONS: Corneal irregular astigmatism after PRK significantly influences contrast sensitivity.

Adult↗
PubMed2001

Piggyback foldable intraocular lens implantation in patients with microphthalmos.

PURPOSE: To evaluate the clinical results of phacoemulsification and implantation of 2 foldable acrylic intraocular lenses (IOLs) in microphthalmic eyes. SETTING: University of Tokyo School of Medicine, Tokyo, Eguchi Eye Hospital, Hakodate, and Osaka Rosai Hospital, Osaka, Japan. METHODS: This study comprised 5 eyes of 3 patients whose manifest spherical equivalent was +10.5 to +18.0 diopters (D) and axial length was 15.79 to 16.82 mm. After phacoemulsification, 2 foldable acrylic IOLs with a mean power of +43.0 D +/- 9.5 (SD) (range +32.0 to +55.0 D) were implanted in the capsular bag. RESULTS: There were no significant intraoperative complications, and there was significant improvement in uncorrected and best corrected visual acuities after surgery. The spherical equivalent decreased significantly; however, the postoperative refraction was considerably more hyperopic than predicted in all eyes. Except for posterior synechias in 2 eyes and slight interlenticular opacification in 2 eyes, no major postoperative complications occurred during the mean follow-up of 14.8 months. CONCLUSIONS: Implanting 2 piggyback IOLs was beneficial in eyes with an extremely short axial length. However, the current system of lens power calculation markedly underestimates the required lens power, resulting in a hyperopic refractive error after surgery. The benefits of in-the-bag placement of 2 foldable lenses are questionable.

Acrylic Resins↗
PubMed2001

Secondary closure of neodymium:YAG laser posterior capsulotomy.

A 67-year-old man reported reduced vision after cataract surgery and neodymium:YAG (Nd:YAG) laser posterior capsulotomy. The diagnosis was complicated due to severe glistenings within the optic of an acrylic foldable intraocular lens (IOL), proliferation of lens epithelial remnants over the capsulotomy opening, and presumed vitreous opacity. Although IOL exchange surgery was considered, a second Nd:YAG laser intervention successfully removed the proliferated lens materials and restored the visual acuity. The glistenings were not the cause of the reduced vision.

Aged↗
PubMed2001

Relation between corneal haze and transforming growth factor-beta1 after photorefractive keratectomy and laser in situ keratomileusis.

PURPOSE: To investigate the relation between corneal haze formation and transforming growth factor-beta (TGF-beta) after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. METHODS: White rabbits were divided into 4 groups, with each group receiving 1 of the following surgeries: manual epithelial abrasion, PRK, lamellar keratotomy, or LASIK. The degree of corneal haze was quantitatively analyzed by measuring the light scattering intensity of corneas before and 4 and 12 weeks after surgery. The expression of type IV collagen and TGF-beta1 in the corneas at baseline and at 4 weeks was examined immunohistochemically. RESULTS: The light scattering intensity was significantly greater 4 and 10 weeks after PRK. In contrast, epithelial abrasion, lamellar keratotomy, and LASIK did not influence the light scattering intensity of the corneas. Type IV collagen was detected in the basal lamina of the corneal epithelium and in Descement's membrane in the normal cornea. After epithelial abrasion, there was no change in the distribution of type IV collagen. Four weeks after PRK, the expression of type IV collagen was detected in the subepithelial layer of the laser-ablated area. Four weeks after lamellar keratotomy, type IV collagen was linearly and fragmentarily detected in the corneal stroma. Four weeks after LASIK, type IV collagen was linearly and continuously detected in the corneal stroma and was detected slightly in the subepithelial region of the laser-ablated area. In the normal corneas, the expression of TGF-beta1 was not detected in the keratocytes. Four weeks after PRK, the expression of TGF-beta1 increased in the keratocytes that proliferated in the subepithelial fibrous layer. In contrast, epithelial abrasion, lamellar keratotomy, and LASIK did not change the expression pattern of TGF-beta1 in the keratocytes. CONCLUSION: The multiplier effect of epithelial abrasion and excimer laser ablation in PRK may increase the expression of TGF-beta1 in keratocytes and induce corneal haze.

Animals↗