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Biomedical subjects

Naoyuki Maeda

Publications and source records attributed to Naoyuki Maeda.

At least 19 recordsLinked to original sources
PubMed2006

Allelic homogeneity in Avellino corneal dystrophy due to a founder effect.

Avellino corneal dystrophy (ACD) is a common corneal dystrophy that shows allelic homogeneity, R124H mutation in the transforming growth factor beta-induced (TGFBI) gene. There are distinct phenotypes of homozygous Avellino corneal dystrophy, termed types I and II. To investigate if the difference is caused by a modifier mutation, we sequenced the entire coding region of TGFBI of two types of ACDs. The sequences obtained from each type were identical, and we could not find any nucleotide alternations. Instead, we found seven single nucleotide polymorphisms (SNPs) compared with the normal control. Primer extension analysis revealed that all 14 homozygous patients were homozygotes in each SNP, which meant that all the patients shared the same disease haplotype. Subsequent analysis of 45 heterozygous ACD patients showed strong linkage disequilibrium between disease alleles of each SNP and ACD. These results strongly suggest that the allelic homogeneity of TGFBI associated corneal dystrophies (ACD, lattice corneal dystrophy types I and III, granular corneal dystrophy and Reis-Bucklers dystrophy) might not be caused by mutation hot spots but by the founder effects.

Alleles↗
PubMed2006

ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.

The objective of the present study was to determine whether a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, pactimibe sulfate (CS-505), could reduce atherosclerotic lesions beyond and independent of the reduction achieved by cholesterol lowering alone from two different types of lesions. (1) Early lesion model. Twelve-week-old apolipoprotein E (apoE)(-/-) mice were treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3% cholestyramine for 12 weeks. Each treatment significantly reduced plasma cholesterol by a similar degree (43-48%). The antiatherosclerotic activity of 0.1% CS-505, however, was more efficacious than the effects of the other treatments (90% versus 40-50%). (2) Advanced lesion model. Twenty-four-week-old apoE(-/-) mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12 weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI-1011 (77% versus 54%), whereas the plasma cholesterol-lowering effect of 0.1% CS-505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical analysis demonstrated that CS-505 significantly reduced the number of macrophages and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This antiatherosclerotic activity is exerted via both cholesterol lowering and direct ACAT inhibition in plaque macrophages.

Animals↗
PubMed2006

Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits.

Novel acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor pactimibe was administered as the sulfate salt form to 3-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits at doses of 0, 10, or 30 mg/kg for 32 weeks. Pactimibe (10 and 30 mg/kg) tended to reduce intimal thickening in thoracic aortic lesions (294+/-39 and 276+/-32 microm, respectively, versus 313+/-37 microm control), histopathological examination revealing significantly increased smooth muscle cell area (12.0+/-0.9% and 12.3+/-0.5%, P<0.05, respectively, versus 9.7+/-0.8% control), significantly increased collagen fiber area (20.5+/-1.2% and 31.0+/-1.3%, P<0.05, respectively, versus 16.2+/-1.0% control), and tended to reduce macrophage infiltration (6.0+/-1.1% and 4.6+/-1.0%, respectively, versus 7.0+/-1.3% control). Pactimibe dose-dependently reduced cholesteryl ester content in thoracic and abdominal aortic lesions, and reduced free cholesterol content in the aorta versus control. Although pactimibe did not alter serum cholesterol levels in WHHL rabbits, it stabilized vulnerable plaque characterized with reduced cholesteryl ester content, enriched collagen fibers and increased smooth muscle cells, indicating potential as a treatment strategy for coronary heart disease.

Animals↗
PubMed2006

Wavefront analysis of eye with monocular diplopia and cortical cataract.

PURPOSE: To determine whether higher-order aberrations can explain the monocular diplopia reported by a patient. DESIGN: Observational case report. METHODS: A patient complaining of monocular diplopia was examined with the Hartmann-Shack aberrometer to determine if the higher-order wavefront aberrations could account for the diplopia. The patient had a mild cortical cataract, and measurements were made before and after lensectomy. In addition, the retinal image was simulated using Zernike polynomials. RESULTS: Spherical aberration (0.20 microm for 4-mm pupil) and secondary astigmatism (-0.12 microm) were increased in the eye. The simulated retinal image had a double configuration that was approximately the same as the subjective image reported by the patient. After cataract surgery, the diplopia disappeared, and the spherical aberrations and secondary astigmatism were considerably decreased. CONCLUSIONS: The monocular diplopia probably stemmed from the combined effects of spherical aberration and secondary astigmatism caused by the cortical cataract.

Adult↗
PubMed2006

Ultrasound biomicroscopic examination of acute hydrops in patients with keratoconus.

PURPOSE: To investigate the possible factors involved in the development of acute hydrops in patients with keratoconus. DESIGN: Prospective interventional case series. METHODS: Thirteen consecutive keratoconic eyes of 13 patients with acute hydrops were examined by ultrasound biomicroscopy (UBM). RESULTS: Ultrasound biomicroscopy (UBM) examinations revealed a rupture of Descemet membrane and intrastromal clefts in all eyes. In 11 of 13 eyes, the intrastromal clefts were connected to the anterior chamber. CONCLUSIONS: Formation of intrastromal clefts may be an important factor in the development of acute hydrops in keratoconic eyes. The clefts may cause severe corneal edema and delay the closure of Descemet membrane during the resolution of corneal edema.

Acute Disease↗
PubMed2006

Paradoxical increase of visual impairment with punctal occlusion in a patient with mild dry eye.

We report a paradoxical increase in visual impairment after punctal plug placement despite improvement in corneal epithelial damage caused by mild dry eye. Ocular higher-order aberrations (HOAs) were measured sequentially with a wavefront sensor before and after punctal plug insertion in a patient with mild dry eye. Although postblink HOAs tend to increase in normal subjects or patients with dry eye, after treatment there was a maximum spike in HOAs for a few seconds that decreased gradually. Excessive retention of tear film by punctal occlusion may cause inferosuperior asymmetrical distribution in precorneal tear-film thickness, possibly leading to slower wavefront on the inferior cornea and increased coma-like aberrations. Increased visual impairment might occur paradoxically despite improvement in the corneal epithelial damage caused by dry eye.

Adult↗
PubMed2006

Wavefront analysis of eyes with cataracts in patients with monocular triplopia.

PURPOSE: To determine whether wavefront analysis using a Hartmann-Shack (H-S) aberrometer can reveal the cause of monocular triplopia in eyes with mild cataracts. METHODS: Six patients (nine eyes; age range 38-58 years; average 49.8 +/- 6.9 years) who complained of monocular triplopia at the Osaka University Hospital between January and December 2003 were examined. Wavefront analyses of ocular and corneal aberrations of the central 4 mm diameter were performed using a H-S aberrometer equipped with a Placido ring videokeratoscope. The ocular and corneal higher-order wavefronts were fitted with a fourth-order Zernike expansion. RESULTS: All nine eyes showed mild nuclear cataract and had a mean spherical refractive error of -10.3 +/- 3.5 D. The visual acuity was > or = 20/40 except in one eye with glaucoma. For the Zernike polynomials, the trefoil aberration (C3-3) and the spherical aberration (C40) were significantly higher than those of age-matched normal controls (p < 0.001). The simulated retinal image of a Landolt C showed that the combination of trefoil aberration and the spherical aberration can cause an image with a triple configuration. CONCLUSIONS: Monocular triplopia was reported by middle-aged patients with mild nuclear cataract and high myopia. Wavefront analyses suggested that the triple configuration was caused by the combined increase of the trefoil and spherical aberration in lenses with mild nuclear cataracts.

Adult↗
PubMed2006

Transplantation of tissue-engineered epithelial cell sheets after excimer laser photoablation reduces postoperative corneal haze.

PURPOSE: To apply tissue-engineered cell sheet transplantation after excimer laser keratectomy as a novel approach for the reduction of postoperative corneal haze. METHODS: Limbal biopsy specimens were obtained, and epithelial cells were cultured on temperature-responsive culture inserts without the use of feeder cells. Laser keratectomy (7.0-mm ablation zone and 160-microm depth) was performed in the contralateral eye, and autologous epithelial cell sheets were transplanted to the ablated corneal stroma. Transplant and control group eyes were assessed by slit lamp biomicroscopy, and corneal haze was scored in a masked fashion, according to the Fantes grading scale. For further examination histologic and immunohistochemical analyses were performed. RESULTS: Tissue-engineered cell sheets produced stable attachment to the laser-ablated sites, resulting in epithelialization, 5 minutes after transplantation. Conversely, control corneas required 3 to 5 days for complete re-epithelialization. At both 1 and 2 months after surgery, corneal haze was significantly inhibited in the transplant group. Histologic analyses showed that the number of keratocytes undergoing apoptosis was decreased in the transplant group at 3 days after surgery. Similarly, the expression of both collagen III and alpha-smooth muscle actin, which may enhance corneal haze, were diminished in the transplant group at 2 months. CONCLUSIONS: The transplantation of tissue-engineered epithelial cell sheets can successfully prevent the development of corneal haze after excimer laser keratectomy.

Actins↗
PubMed2006

Serial measurements of higher-order aberrations after blinking in normal subjects.

PURPOSE: To investigate sequential changes in the optical quality of normal eyes associated with blinking. METHODS: Ocular higher-order aberrations (HOAs) were measured sequentially by using a wavefront sensor for 30 seconds in 20 eyes of 20 normal subjects. During the measurement, subjects were forced to blink every 10 seconds. The obtained aberration data were analyzed in the central 4-mm diameter for coma-like, spherical-like, and total HOAs up to the sixth-order Zernike polynomials. RESULTS: The serial changes in the HOAs with blinking were classified into four groups by pattern: stable (25%), small-fluctuation (45%), sawtooth (20%), and others (10%). In the subjects with the sawtooth pattern, the total HOAs increased significantly (P < 0.001, one-way repeated-measures ANOVA) with time between blinks. Increased total HOAs and coma-like aberrations in the subjects with the sawtooth pattern suggested that the inferosuperior asymmetric change in tear film thickness is responsible. CONCLUSIONS: Dynamic changes in HOAs after blinking showed variations even in clinically normal subjects. Serial measurements of HOAs may be useful in evaluating the dynamic changes in tear film and the effects on the quality of vision after blinking.

Adult↗
PubMed2006

[Clinical study of anterior ocular segment topography in angle-closure glaucoma using the three-dimensional anterior segment analyzer Pentacam].

PURPOSE: The anterior ocular segment topography in angle-closure glaucoma was studied using the non-contact three-dimensional anterior segment analyzer Pentacam. SUBJECTS AND METHODS: The central anterior chamber (AC) depth, mid-peripheral AC depth, peripheral AC depth, AC volume, central AC depth/ocular axial length ratio and angles of a narrow angle group (47 eyes of 29 patients), a post laser iridotomy (LI) group (43 eyes of 30 patients), and an open-angle glaucoma (OAG) group (37 eyes of 21 patients) were measured and compared. In addition, changes in the parameters before and after LI (13 eyes of 9 patients) were investigated. RESULTS: The AC volume for the narrow angle group (74.5 +/- 21.1 microl) was significantly smaller than for the other groups (post LI group: 96.4 +/- 21.4 microl; OAG group: 144.2 +/- 31.6 microl, p<0.001). The most significant association was detected between AC volume and the peripheral AC depth. Only two parameters, AC volume and peripheral AC depth, increased significantly after LI (p< 0.001). DISCUSSION: Measurement of the AC volume and the peripheral AC depth using Pentacam is useful for evaluating the anterior ocular segment topography in narrow angle eyes.

Aged↗
PubMed2005

Functional human corneal endothelial cell sheets harvested from temperature-responsive culture surfaces.

This study reports a new method for fabricating bioengineered human corneal endothelial cell sheets suitable for ocular surgery and repair. We have initially cultured human corneal endothelial cells on type IV collagen-coated dishes and, after several passages, expanded cells were then seeded onto novel temperature-responsive culture dishes. Four weeks after reaching confluence, these cultured endothelial cells were harvested as intact monolayer cell sheets by simple temperature reduction without enzymatic treatment. Scanning electron microscopy indicated that these cells were primarily hexagonal with numerous microvilli and cilia, similar to the native corneal endothelium. The Na+, K+-ATPase pump sites were located at the cell borders as in vivo. Moreover, cell densities and numbers of pump sites were identical to those of in vivo human corneal endothelium under optimized conditions. A 3H-ouabain binding analysis demonstrated a linear proportionality for cell pump density between confluent cell densities of 575 cells/mm2 and 3070 cells/mm2. We also confirmed Na+, K+-ATPase activity in the sheets in vitro. Xenograft transplantation results showed that the fabricated sheets retain their function of maintaining proper stromal hydration in vivo. We have established a regimen to culture and proliferate human corneal endothelial cells and fabricate endothelial sheets ex vivo morphologically and functionally similar to the native corneal endothelium. Our results support the value of harvested cell sheets for clinical applications in ocular reconstructive surgery in patients with ocular endothelial decompensation.

Cell Culture Techniques↗
PubMed2005

Rheumatoid arthritis-associated corneal ulceration complicated by bacterial infection.

We report two cases of rheumatoid ocular disease complicated by infection of methicillin-sensitive Staphylococcus aureus (MSSA) in one case, and methicillin-resistant Staphylococcus aureus (MRSA) in the other. In both cases, punctal occlusion and immunosuppressive therapy were presumed to be major risk factors of the infections. In addition, the characteristic feature was corneal melting, which is probably accelerated by infection. To avoid infectious progression and melting, potent antibiotics followed by immunosuppressive therapy were necessary.

Journal Article↗
PubMed2005

Transient keratectasia caused by intraocular pressure elevation after laser in situ keratomileusis.

Transient keratectasia developed in association with a marked intraocular pressure (IOP) elevation in a 26-year-old man who had laser in situ keratomileusis (LASIK) for myopia of -9.0 diopters. The keratectasia subsided promptly after the IOP was normalized by an intravenous administration of mannitol. Keratectasia did not recur. Intraocular pressure elevation can cause keratectasia in a structurally compromised cornea after LASIK.

Adult↗
PubMed2005

Ocular surface reconstruction using autologous rabbit oral mucosal epithelial sheets fabricated ex vivo on a temperature-responsive culture surface.

PURPOSE: Autologous stem cell transplantation for total limbal stem cell deficiency is immunologically preferable, to avoid allograft rejection. This study was undertaken to investigate the possibility of a novel tissue engineering approach for ocular surface reconstruction, using autologous oral mucosal epithelial stem cells expanded ex vivo on temperature-responsive cell culture surfaces. METHODS: Rabbit oral mucosal epithelial cells cultured on temperature-responsive culture surfaces with mitomycin-C-treated 3T3 feeder cells for 2 weeks produced confluent epithelial cell sheets. Putative progenitor cell populations were estimated by colony-forming assays. Autologous transplantation of these cell sheets to surgically manipulated eyes was performed, and ocular surface reconstruction and cell phenotypic modulation were examined. RESULTS: All cultured oral epithelial cells were nonenzymatically harvested as transplantable intact cell sheets by reducing culture temperature to 20 degrees C. Oral epithelial cells were stratified in three to five cell layers more similar to corneal epithelium than to oral mucosal epithelium. Colony-forming assays and immunofluorescence for p63, beta1-integrin, and connexin 43 indicated retention of viable stem and/or progenitor cell populations in cell sheets. Autologous transplantation to rabbit corneal surfaces successfully reconstructed the corneal surface, with restoration of transparency. Four weeks after transplantation, epithelial stratification was similar to that in the corneal epithelium, although the keratin expression profile retained characteristics of the oral mucosal epithelium. CONCLUSIONS: Cell sheet harvest technology enables fabrication of viable, transplantable, tissue-engineered epithelial cell sheets that retain putative progenitor cells from autologous oral mucosal epithelial cells. Promising clinical capabilities for autologous tissue-engineered epithelial cell sheets for ocular surface reconstruction are indicated.

Animals↗
PubMed2004

Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium.

BACKGROUND: Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface. METHODS: We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surface, sheets of cultured autologous cells that had been harvested with a simple reduced-temperature treatment were transplanted directly to the denuded corneal surfaces (one eye of each patient) without sutures. RESULTS: Complete reepithelialization of the corneal surfaces occurred within one week in all four treated eyes. Corneal transparency was restored and postoperative visual acuity improved remarkably in all four eyes. During a mean follow-up period of 14 months, all corneal surfaces remained transparent. There were no complications. CONCLUSIONS: Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.

Aged↗
PubMed2004

Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2.

Many types of organ-specific stem cells have been recently shown to exhibit a side population (SP) phenotype based on their ability to efflux Hoechst 33342 dye. Because stem cells from corneal epithelium reside in the basal layer of the limbal epithelium, the purpose of this study was to examine whether the limbal epithelium contains SP cells. The ATP-binding cassette transporter Bcrp1/ABCG2 is reported to contribute to the SP phenotype in cells from several diverse sources. Here we show data from fluorescence-activated cell sorting and real-time quantitative RT-PCR analysis showing that harvested limbal epithelial cells contain SP cells expressing ABCG2. Immunofluorescence revealed that a portion of limbal epithelial basal cells expressed ABCG2. Data indicate that ABCG2 positive limbal epithelial cells are putative corneal epithelial stem cells.

Adenosine Triphosphate↗
PubMed2004

Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface.

BACKGROUND: Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and visual loss. Recent attempts have been made to fabricate corneal epithelial graft constructs, but the technology is still evolving. We have developed a novel cell-sheet manipulation technology using temperature-responsive culture surfaces to generate functional, cultivated corneal epithelial cell sheet grafts. METHODS: Human or rabbit limbal stem cells were cocultured with mitomycin C-treated 3T3 feeder layers on temperature-responsive culture dishes at 37 degrees C. Cell sheets were harvested from the dishes after 2 weeks by reducing temperature to 20 degrees C. Histologic analyses, immunoblotting, and colony-forming assay were performed to characterize the cell sheets. Autologous transplantation was undertaken to reconstruct the corneal surfaces of rabbits with experimentally induced limbal stem cell deficiencies. RESULTS: Multilayered corneal epithelial sheets were harvested intact simply by reducing the temperature, without the use of proteases. Cell-cell junctions and extracellular matrix on the basal side of the sheet, critical to sheet integrity and function, remained intact. A viable population of corneal progenitor cells, close in number to that originally seeded, was found in the sheets. Harvested sheets were easily manipulated, transplantable without any carriers, and readily adhesive to corneal stroma so that suturing was not required. Corneal surface reconstruction in rabbits was highly successful. CONCLUSIONS: Cell sheet engineering technology allows us to create intact, transplantable corneal epithelial cell sheets that retain stem cells from limbal stem cells expanded ex vivo. Our research indicates highly promising clinical capabilities for our bioengineered corneal epithelial sheet.

3T3 Cells↗